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Kadoglou NPE, Stasinopoulou M, Velidakis N, Khattab E, Christodoulou E, Gkougkoudi E, Valsami G. The Complex Mechanisms and the Potential Effects of Statins on Vascular Calcification: A Narrative Review. Rev Cardiovasc Med 2024; 25:51. [PMID: 39077343 PMCID: PMC11263155 DOI: 10.31083/j.rcm2502051] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/20/2023] [Accepted: 10/25/2023] [Indexed: 07/31/2024] Open
Abstract
Vascular calcification (VC) is a complex process of calcium deposition on the arterial wall and atherosclerotic plaques and involves interaction between vascular smooth muscle cells, inflammatory and VC mediators. The latter are independent predictors of cardiovascular morbidity and mortality and potential targets of pharmaceutical therapy. This paper is a narrative review of the complex mechanisms of VC development and in this context the potential anti-atherosclerotic effects of statins. At the initial stages of atherosclerosis VC correlates with atherosclerosis burden and in the long-term with cardiovascular morbidity and mortality. A plethora of animal and clinical studies have proposed statins as the cornerstone of primary and secondary prevention of atherosclerotic cardiovascular disease. Based on coronary computed tomography data, high doses of statins may have negligible or even positive effects on the progression of coronary artery calcification. Growing data support an increase in atherosclerotic plaque calcification in peripheral arteries (e.g., carotids), after long-term, statin-therapy. Despite the paradox of increasing VC, those effects of statins have been associated with higher plaque stability, reducing the risk of consequent adverse events. Statins seem to promote a "favorable" atherosclerotic calcification, suppressing atherosclerotic lesion expansion and their vulnerability. More studies are required to clarify the underlying mechanisms.
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Affiliation(s)
| | - Marianna Stasinopoulou
- Center of Clinical, Experimental Surgery, and Translational Research, Biomedical Research Foundation, Academy of Athens, 11527 Athens, Greece
| | | | - Elina Khattab
- Medical School, University of Cyprus, 2029 Nicosia, Cyprus
| | - Eirini Christodoulou
- Laboratory of Biopharmaceutics-Pharmacokinetics, Department of Pharmacy, School of Health Sciences, National & Kapodistrian University of Athens, 15784 Athens, Greece
| | | | - Georgia Valsami
- Laboratory of Biopharmaceutics-Pharmacokinetics, Department of Pharmacy, School of Health Sciences, National & Kapodistrian University of Athens, 15784 Athens, Greece
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Cambray S, Bermúdez-López M, Garcia-Carrasco A, Valdivielso JM. Matrix Gla protein polymorphism rs1800802 is associated with atheroma plaque progression and with cardiovascular events in a chronic kidney disease cohort. Clin Kidney J 2024; 17:sfad257. [PMID: 38186884 PMCID: PMC10768782 DOI: 10.1093/ckj/sfad257] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Indexed: 01/09/2024] Open
Abstract
Background Chronic kidney disease (CKD) is associated with increased atherosclerotic burden and higher risk for cardiovascular events (CVE). Atherosclerosis has a significant genetic component and, in CKD, it is influenced by mineral metabolism alterations. Therefore, genetic modifications of mineral metabolism-related proteins could affect atherosclerosis in CKD patients. In the present study we investigated the role of single nucleotide polymorphisms (SNPs) of the matrix gamma-carboxy glutamic acid protein (MGP) on atherosclerosis progression and CVE in a CKD cohort. Methods A total of 2187 CKD patients from the Observatorio Nacional de Aterosclerosis en Nefrologia (NEFRONA) study were genotyped for SNPs present in the matrix gamma-carboxy glutamic acid (Gla) protein (MGP) gene. Atheromatosis was detected by vascular ultrasound. Progression of atheromatosis, defined as an increase in territories with plaque, was assessed after 24 months. Patients were followed for 48 months for CVE. Association of SNPs with plaque progression was assessed by logistic regression and their capacity to predict CVE by Cox regression. Results Three SNPs of the MGP gene were analyzed. No association of the rs4236 or the rs1800801 SNPs was detected with any of the outcomes. However, patients homozygotes for the minor allele of the rs1800802 SNP showed higher adjusted risk for plaque progression [odds ratio 2.3 (95% confidence interval 1.06-4.9)] and higher risk of suffering a CVE [hazard ratio 2.16 (95% confidence interval 1.13-4.12)] compared with the rest of genotypes. No association of the SNP with total or dp-ucMGP levels was found in a subsample. Conclusions The rs1800802 polymorphism of MGP is associated with plaque progression and CVE in CKD patients.
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Affiliation(s)
- Serafí Cambray
- Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida Fundació Dr Pifarré (IRBLleida)
- Department of Basic Medical Sciences, University of Lleida, Lleida, Spain
| | - Marcelino Bermúdez-López
- Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida Fundació Dr Pifarré (IRBLleida)
- Department of Experimental Medicine, University of Lleida, Lleida, Spain
| | - Alicia Garcia-Carrasco
- Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida Fundació Dr Pifarré (IRBLleida)
| | - Jose M Valdivielso
- Vascular and Renal Translational Research Group, Biomedical Research Institute of Lleida Fundació Dr Pifarré (IRBLleida)
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Azegami T, Kounoue N, Sofue T, Yazawa M, Tsujita M, Masutani K, Kataoka Y, Oguchi H. Efficacy of pre-emptive kidney transplantation for adults with end-stage kidney disease: a systematic review and meta-analysis. Ren Fail 2023; 45:2169618. [PMID: 36705051 PMCID: PMC9888453 DOI: 10.1080/0886022x.2023.2169618] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Pre-emptive kidney transplantation (PEKT), i.e., transplantation performed before initiation of maintenance dialysis, is considered an ideal renal replacement therapy because there is no exposure to long-term dialysis therapy. Therefore, we summarized advantages/disadvantages of PEKT to assist in deciding whether kidney transplantation should be performed pre-emptively. METHODS This study was registered with PROSPERO, CRD42021269163. Observational studies comparing clinical outcomes between PEKT and non-PEKT were included; those involving only pediatric recipients or simultaneous multi-organ transplantations were excluded. The PubMed/MEDLINE, Cochrane Library, and Ichushi-Web databases were searched on 1 August 2021. Studies were pooled using the generic inverse-variance method with random effects model, and risk of bias was assessed using ROBINS-I. RESULTS Seventy-six studies were included in the systematic review (sample size, 23-121,853; enrollment year, 1968-2019). PEKT patients had lower all-cause mortality (adjusted HR: 0.78 [95% CI 0.66-0.92]), and lower death-censored graft failure (0.81 [0.67-0.98]). Unadjusted RRs for the following outcomes were comparable between the two patient groups: cardiovascular disease, 0.90 (0.58-1.40); biopsy-proven acute rejection, 0.75 (0.55-1.03); cytomegalovirus infection, 1.04 (0.85-1.29); and urinary tract infection, 0.89 (0.61-1.29). Mean differences in post-transplant QOL score were comparable in both groups. The certainty of evidence for mortality and graft failure was moderate and that for other outcomes was very low following the GRADE classification. CONCLUSIONS The present meta-analysis shows the potential benefits of PEKT, especially regarding patient and graft survival, and therefore PEKT is recommended for adults with end-stage kidney disease.
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Affiliation(s)
- Tatsuhiko Azegami
- Keio University Health Center, Yokohama, Japan,Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
| | - Noriyuki Kounoue
- Department of Nephrology, Toho University Faculty of Medicine, Tokyo, Japan
| | - Tadashi Sofue
- Department of Cardiovascular and Cerebrovascular Medicine, Kagawa University, Takamatsu, Japan
| | - Masahiko Yazawa
- Department of Nephrology and Hypertension, St Marianna University School of Medicine, Kawasaki, Japan
| | - Makoto Tsujita
- Department of Nephrology, Masuko Memorial Hospital, Nagoya, Japan
| | - Kosuke Masutani
- Department of Internal Medicine, Faculty of Medicine, Division of Nephrology and Rheumatology, Fukuoka University, Fukuoka, Japan
| | - Yuki Kataoka
- Department of Internal Medicine, Kyoto Min-Iren Asukai Hospital, Kyoto, Japan,Scientific Research Works Peer Support Group (SRWS-PSG), Osaka, Japan,Department of Community Medicine, Section of Clinical Epidemiology, Kyoto University Graduate School of Medicine, Kyoto, Japan,Department of Healthcare Epidemiology, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan
| | - Hideyo Oguchi
- Department of Nephrology, Toho University Faculty of Medicine, Tokyo, Japan,CONTACT Hideyo Oguchi Department of Nephrology, Toho University Faculty of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo143-8541, Japan
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Fujita N, Hatakeyama S, Momota M, Tobisawa Y, Yoneyama T, Okamoto T, Yamamoto H, Yoneyama T, Hashimoto Y, Yoshikawa K, Ohyama C. Association between Aortic Calcification Burden and the Severity of Erectile Dysfunction in Men Undergoing Dialysis: A Cross-Sectional Study. World J Mens Health 2023; 41:373-381. [PMID: 35791298 PMCID: PMC10042658 DOI: 10.5534/wjmh.210230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 12/26/2021] [Accepted: 01/15/2022] [Indexed: 11/15/2022] Open
Abstract
PURPOSE Accelerated atherosclerosis is a major complication in patients with end-stage renal disease and it plays an important role in the pathogenesis of erectile dysfunction (ED). However, the association between aortic calcification burden and the severity of ED remains unclear. The aim of the present study was to investigate this association in men undergoing dialysis. MATERIALS AND METHODS This cross-sectional study included 71 men undergoing peritoneal dialysis and/or hemodialysis between July 2016 and May 2018 at Mutsu General Hospital. ED was assessed with the Sexual Health Inventory for Men (SHIM). Patients were divided into the mild/moderate (SHIM score ≥8) and severe ED groups (SHIM score ≤7). Aortic calcification index (ACI) was examined as a clinical indicator of abdominal aortic calcification. Multivariable logistic regression analysis was performed to identify the significant factors associated with severe ED. RESULTS The median age of the study participants was 64 years; all had ED, with 64.8% having severe ED. In the multivariable analyses, a slight association was observed between ankle-brachial index and severe ED (odds ratio [OR], 0.058; p=0.072), whereas ACI was significantly associated with severe ED (OR, 1.022; p=0.022). CONCLUSIONS Aortic calcification burden was independently associated with severe ED.
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Affiliation(s)
- Naoki Fujita
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Shingo Hatakeyama
- Department of Advanced Blood Purification Therapy, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
| | - Masaki Momota
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Yuki Tobisawa
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Tohru Yoneyama
- Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Teppei Okamoto
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Hayato Yamamoto
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Takahiro Yoneyama
- Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Yasuhiro Hashimoto
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | | | - Chikara Ohyama
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
- Department of Advanced Blood Purification Therapy, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
- Department of Advanced Transplant and Regenerative Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
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Guo G, Zhou J, Xu T, Sheng Z, Huang A, Sun L, Yao L. Effect of Magnesium Supplementation on Chronic Kidney Disease-Mineral and Bone Disorder in Hemodialysis Patients: A Meta-Analysis of Randomized Controlled Trials. J Ren Nutr 2021; 32:102-111. [PMID: 34531112 DOI: 10.1053/j.jrn.2021.07.009] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 06/27/2021] [Accepted: 07/26/2021] [Indexed: 11/11/2022] Open
Abstract
OBJECTIVES Research about the effects of magnesium (Mg) supplementation on chronic kidney disease-mineral bone disorder (CKD-MBD) among hemodialysis (HD) patients is controversial. Thus, we conducted a meta-analysis to examine Mg supplementation's effects on CKD-MBD in patients requiring dialysis. METHODS The PubMed and EMBASE databases were searched for English language studies up to September 2020. The main indicators of our study were changes in serum Mg, calcium (Ca), phosphate, parathyroid hormone (PTH), and C-reactive protein levels, and carotid intima-media thickness (CIMT) after Mg supplementation. Mg efficacy was evaluated by weighted mean difference (WMD) and confidence intervals (CIs), and subgroup analyses of intervention type and intervention duration were also performed. RESULTS Eight eligible studies comprising 309 HD patients were included in our meta-analysis. Mg supplementation alone produced a negative effect on serum PTH levels (WMD = -236.56; 95% CI -349.71 to -123.41) and CIMT (WMD = -0.18; 95% CI -0.34 to -0.01). A subgroup analysis based on intervention type showed a significant improvement in serum Mg (WMD = 1.08; 95% CI 0.51-1.64) and Ca (WMD = -0.50; 95% CI -0.77 to -0.23) levels when Mg was administered via dialysate and oral medication, respectively. Different intervention durations had no effect on serum Mg levels. Mg supplementation had no significant effect on serum phosphate (WMD = -0.25; 95% CI -0.64 to 0.14) and C-reactive protein levels (WMD = -0.02; 95% CI -2.80 to 2,76). CONCLUSIONS Our results showed that Mg supplementation alone could improve CKD-MBD by regulating serum Ca and PTH metabolism and decreasing CIMT among HD patients.
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Affiliation(s)
- Guangying Guo
- Department of Nephrology, the First Hospital of China Medical University, Shenyang, China
| | - Junlei Zhou
- Department of Nephrology, the First Hospital of China Medical University, Shenyang, China
| | - Tianhua Xu
- Department of Nephrology, the First Hospital of China Medical University, Shenyang, China
| | - Zitong Sheng
- Department of Nephrology, the First Hospital of China Medical University, Shenyang, China
| | - Aoran Huang
- Department of Nephrology, the First Hospital of China Medical University, Shenyang, China
| | - Li Sun
- Department of Nephrology, the First Hospital of China Medical University, Shenyang, China.
| | - Li Yao
- Department of Nephrology, the First Hospital of China Medical University, Shenyang, China.
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Wu PY, Lee SY, Chang KV, Chao CT, Huang JW. Gender-Related Differences in Chronic Kidney Disease-Associated Vascular Calcification Risk and Potential Risk Mediators: A Scoping Review. Healthcare (Basel) 2021; 9:979. [PMID: 34442116 PMCID: PMC8394860 DOI: 10.3390/healthcare9080979] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 07/26/2021] [Accepted: 07/28/2021] [Indexed: 12/13/2022] Open
Abstract
Vascular calcification (VC) involves the deposition of calcium apatite in vascular intima or media. Individuals of advanced age, having diabetes mellitus or chronic kidney disease (CKD) are particularly at risk. The pathogenesis of CKD-associated VC evolves considerably. The core driver is the phenotypic change involving vascular wall constituent cells toward manifestations similar to that undergone by osteoblasts. Gender-related differences are observed regarding the expressions of osteogenesis-regulating effectors, and presumably the prevalence/risk of CKD-associated VC exhibits gender-related differences as well. Despite the wealth of data focusing on gender-related differences in the risk of atherosclerosis, few report whether gender modifies the risk of VC, especially CKD-associated cases. We systematically identified studies of CKD-associated VC or its regulators/modifiers reporting data about gender distributions, and extracted results from 167 articles. A significantly higher risk of CKD-associated VC was observed in males among the majority of original investigations. However, substantial heterogeneity exists, since multiple large-scale studies yielded neutral findings. Differences in gender-related VC risk may result from variations in VC assessment methods, the anatomical segments of interest, study sample size, and even the ethnic origins of participants. From a biological perspective, plausible mediators of gender-related VC differences include body composition discrepancies, alterations involving lipid profiles, inflammatory severity, diversities in matrix Gla protein (MGP), soluble Klotho, vitamin D, sclerostin, parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), and osteoprotegerin levels. Based on our findings, it may be inappropriate to monotonously assume that male patients with CKD are at risk of VC compared to females, and we should consider more background in context before result interpretation.
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Affiliation(s)
- Patrick Yihong Wu
- School of Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan;
| | - Szu-Ying Lee
- Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County 640, Taiwan; (S.-Y.L.); (J.-W.H.)
| | - Ke-Vin Chang
- Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital BeiHu Branch, Taipei 10845, Taiwan;
| | - Chia-Ter Chao
- Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei 100233, Taiwan
- Nephrology Division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan
- Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital BeiHu Branch, Taipei 10845, Taiwan
| | - Jenq-Wen Huang
- Nephrology Division, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County 640, Taiwan; (S.-Y.L.); (J.-W.H.)
- Nephrology Division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 100233, Taiwan
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Bover J, Aguilar A, Arana C, Molina P, Lloret MJ, Ochoa J, Berná G, Gutiérrez-Maza YG, Rodrigues N, D'Marco L, Górriz JL. Clinical Approach to Vascular Calcification in Patients With Non-dialysis Dependent Chronic Kidney Disease: Mineral-Bone Disorder-Related Aspects. Front Med (Lausanne) 2021; 8:642718. [PMID: 34095165 PMCID: PMC8171667 DOI: 10.3389/fmed.2021.642718] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 04/12/2021] [Indexed: 12/13/2022] Open
Abstract
Chronic kidney disease (CKD) is associated with a very high morbimortality, mainly from cardiovascular origin, and CKD is currently considered in the high- or very high risk- cardiovascular risk category. CKD-mineral and bone disorders (CKD-MBDs), including vascular and/or valvular calcifications, are also associated with these poor outcomes. Vascular calcification (VC) is very prevalent (both intimal and medial), even in non-dialysis dependent patients, with a greater severity and more rapid progression. Simple X-ray based-scores such as Adragão's (AS) are useful prognostic tools and AS (even AS based on hand-X-ray only) may be superior to the classic Kauppila's score when evaluating non-dialysis CKD patients. Thus, in this mini-review, we briefly review CKD-MBD-related aspects of VC and its complex pathophysiology including the vast array of contributors and inhibitors. Furthermore, although VC is a surrogate marker and is not yet considered a treatment target, we consider that the presence of VC may be relevant in guiding therapeutic interventions, unless all patients are treated with the mindset of reducing the incidence or progression of VC with the currently available armamentarium. Avoiding phosphate loading, restricting calcium-based phosphate binders and high doses of vitamin D, and avoiding normalizing (within the normal limits for the assay) parathyroid hormone levels seem logical approaches. The availability of new drugs and future studies, including patients in early stages of CKD, may lead to significant improvements not only in patient risk stratification but also in attenuating the accelerated progression of VC in CKD.
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Affiliation(s)
- Jordi Bover
- Department of Nephrology, Fundació Puigvert, IIB Sant Pau, Universitat Autònoma, REDinREN, Barcelona, Spain
| | - Armando Aguilar
- Department of Nephrology, Instituto Mexicano del Seguro Social, Hospital General de Zona No. 2, Tuxtla Gutiérrez, Mexico
| | - Carolt Arana
- Department of Nephrology, Fundació Puigvert, IIB Sant Pau, Universitat Autònoma, REDinREN, Barcelona, Spain
| | - Pablo Molina
- Department of Nephrology, Hospital Universitario Dr Peset, Universidad de Valencia, REDinREN, Valencia, Spain
| | - María Jesús Lloret
- Department of Nephrology, Fundació Puigvert, IIB Sant Pau, Universitat Autònoma, REDinREN, Barcelona, Spain
| | - Jackson Ochoa
- Department of Nephrology, Fundació Puigvert, IIB Sant Pau, Universitat Autònoma, REDinREN, Barcelona, Spain
| | - Gerson Berná
- Department of Nephrology, Fundació Puigvert, IIB Sant Pau, Universitat Autònoma, REDinREN, Barcelona, Spain
| | - Yessica G. Gutiérrez-Maza
- Department of Nephrology, Instituto Mexicano del Seguro Social, Hospital General de Zona No. 2, Tuxtla Gutiérrez, Mexico
| | - Natacha Rodrigues
- Division of Nephrology and Renal Transplantation, Department of Medicine, Centro Hospitalar Universitário Lisboa Norte, EPE, Lisboa, Portugal
| | - Luis D'Marco
- Servicio de Nefrología, Hospital Clínico Universitario, INCLIVA, Universidad de Valencia, Valencia, Spain
| | - José L. Górriz
- Servicio de Nefrología, Hospital Clínico Universitario, INCLIVA, Universidad de Valencia, Valencia, Spain
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Zhao S, Cao J, Li J, Yang X, Cao P, Lan J, Lu G. Association between serum elastin-derived peptides and abdominal aortic calcification in peritoneal dialysis patients: a cross-sectional study. Ren Fail 2021; 43:860-868. [PMID: 33993833 PMCID: PMC8143601 DOI: 10.1080/0886022x.2021.1918163] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background Peritoneal dialysis (PD) patients experience accelerated arterial aging, which is characterized by elastin degradation. Elastin-derived peptides (EDPs) are direct products of elastin fragmentation. This study tried to explore the association between serum EDPs and abdominal aortic calcification (AAC) in PD patients. Methods Serum levels of EDPs were analyzed in 126 eligible PD patients and 30 controls. PD patients were grouped according to the annularity of AAC evaluated by an abdominal computed tomography (CT) scan. Serum EDPs were analyzed in relation to the presence of AAC or severe AAC in PD patients by logistic regression analysis. Results Serum EDPs in PD patients were significantly higher than age-matched controls. In 126 PD patients, higher EDPs was associated with greater risk of present AAC (OR = 1.056, 95%CI 1.010–1.103) and severe AAC (OR = 1.062, 95%CI 1.004–1.123). A combination of EDPs substantially improved the accuracy of diagnostic performance for AAC and severe AAC. Conclusions EDPs can predict the presence and extent of AAC in PD patients, indicating its possible role to recognize PD patients at risk for AAC and severe AAC.
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Affiliation(s)
- Shizhu Zhao
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jingyuan Cao
- Department of Nephrology, Taizhou People's hospital, The Fifth Affiliated Hospital of Nantong University, Taizhou, China
| | - Jianzhong Li
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiaochun Yang
- Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Peiyang Cao
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Jingjing Lan
- Department of Nephology, Wuxi Traditional Chinese Medicine Hospital, Wuxi, China
| | - Guoyuan Lu
- Department of Nephrology, The First Affiliated Hospital of Soochow University, Suzhou, China
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Mukai H, Dai L, Chen Z, Lindholm B, Ripsweden J, Brismar TB, Heimbürger O, Barany P, Qureshi AR, Söderberg M, Bäck M, Stenvinkel P. Inverse J-shaped relation between coronary arterial calcium density and mortality in advanced chronic kidney disease. Nephrol Dial Transplant 2020; 35:1202-1211. [PMID: 30534995 DOI: 10.1093/ndt/gfy352] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 09/28/2018] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The coronary artery calcium (CAC) score from cardiac computed tomography (CT) is a composite of CAC volume and CAC density. In the general population, CAC volume is positively and CAC density inversely associated with cardiovascular disease (CVD) events, implying that decreased CAC density reflects atherosclerotic plaque instability. We analysed associations of CAC indices with mortality risk in patients with end-stage renal disease [chronic kidney disease Stage 5 (CKD5)]. METHODS In 296 CKD5 patients undergoing cardiac CT (median age 55 years, 67% male, 19% diabetes, 133 dialysed), the Framingham risk score (FRS), presence of CVD and protein-energy wasting (PEW; subjective global assessment) and high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were determined at baseline. During follow-up for a median of 35 months, 51 patients died and 75 patients underwent renal transplantation. All-cause mortality risk was analysed with competing-risk regression models. Vascular calcification was analysed in biopsies of the arteria epigastrica inferior in 111 patients. RESULTS Patients in the middle tertile of CAC density had the highest CAC score, CAC volume, age, CVD, PEW, FRS, hsCRP and IL-6. In competing risk analysis, the middle {subhazard ratio [sHR] 10.7 [95% confidence interval (CI) 2.0-57.3]} and high [sHR 8.9 (95% CI 1.5-51.8)] tertiles of CAC density associated with increased mortality, independent of CAC volume. The high tertile of CAC volume, independent of CAC density, associated with increased mortality [sHR 8.9 (95% CI 1.5-51.8)]. Arterial media calcification was prominent and associated with CAC volume and CAC density. CONCLUSIONS In CKD5, mortality increased linearly with higher CAC score and CAC volume whereas for CAC density an inverse J-shaped pattern was observed, with the crude mortality rate being highest for the middle tertile of CAC density. CAC volume and CAC density were associated with the extent of arterial media calcification.
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Affiliation(s)
- Hideyuki Mukai
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Lu Dai
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Zhimin Chen
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Bengt Lindholm
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Jonaz Ripsweden
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Torkel B Brismar
- Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Olof Heimbürger
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Peter Barany
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Abdul Rashid Qureshi
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
| | - Magnus Söderberg
- Department of Pathology, Drug Safety and Metabolism, AstraZeneca, Mölndal, Sweden
| | - Magnus Bäck
- Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
| | - Peter Stenvinkel
- Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Campus Flemingsberg, Stockholm, Sweden
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10
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Elhabashi AF, Sulaibeekh L, Seddiq N, Alali S, Abdulmajeed AK, Perez NS. Presepsin Level Correlates with the Development of Moderate Coronary Artery Calcifications in Hemodialysis Patients: A Preliminary Cross-Section Design Study. Risk Manag Healthc Policy 2020; 13:999-1006. [PMID: 32821182 PMCID: PMC7422906 DOI: 10.2147/rmhp.s262058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 07/22/2020] [Indexed: 11/23/2022] Open
Abstract
Purpose End-stage renal disease patients have a high mortality rate linked to cardiovascular complications, and one of these complications is vascular calcification. This study was performed to test if presepsin, an inflammatory marker, is a predictor of coronary artery calcification (CAC) in hemodialysis (HD) patients. Patients and Methods This study was a cross-sectional design involving 48 HD patients and 13 control subjects. Coronary artery calcification score (CACs) was evaluated by a high resolution, ECG synchronized computed tomography of the heart using a CT calcium scoring. Presepsin and other laboratory analyses were performed on blood samples drawn before HD. Results Presepsin levels in HD patients were 14 times higher than healthy controls (P<0.01). Also, all laboratory tests except for vitamin D were significantly different than controls. Presepsin, phosphorus levels, and calcium-phosphate product were positively correlated with increasing CACs within groups of zero to moderate calcifications (p<0.05, R=0.459 and <0.01, R=0.591, respectively). These correlations were not seen with eGFR, PTH, calcium, vitamin D, CRP, or ESR levels. Furthermore, the log-transformed data of presepsin correlated with 1–15 months of HD vintage (p<0.05, R=0.482), whereas CACs data correlated with 1–20 months of HD vintage (p<0.05, R=0.425). Conclusion Although this study is preliminary and has a limited number of patients, it shows that presepsin, as an inflammatory marker, correlates with the development of moderate CAC in HD patients and may predict CAC development. Therefore, measuring presepsin and managing inflammation before and during the early phases of HD may lower coronary calcification development. However, more clinical studies in this direction are essential.
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Affiliation(s)
- Ahmed F Elhabashi
- Bahrain Defense Force Hospital, Royal Medical Services, Riffa, Kingdom of Bahrain
| | - Leena Sulaibeekh
- Bahrain Defense Force Hospital, Royal Medical Services, Riffa, Kingdom of Bahrain
| | - Nahed Seddiq
- Bahrain Defense Force Hospital, Royal Medical Services, Riffa, Kingdom of Bahrain
| | - Salman Alali
- Bahrain Defense Force Hospital, Royal Medical Services, Riffa, Kingdom of Bahrain
| | - Amjad K Abdulmajeed
- Bahrain Defense Force Hospital, Royal Medical Services, Riffa, Kingdom of Bahrain
| | - Nuria S Perez
- Bahrain Defense Force Hospital, Royal Medical Services, Riffa, Kingdom of Bahrain
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11
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Chen W, Anokhina V, Dieudonne G, Abramowitz MK, Kashyap R, Yan C, Wu TT, de Mesy Bentley KL, Miller BL, Bushinsky DA. Patients with advanced chronic kidney disease and vascular calcification have a large hydrodynamic radius of secondary calciprotein particles. Nephrol Dial Transplant 2020; 34:992-1000. [PMID: 29788425 DOI: 10.1093/ndt/gfy117] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND The size of secondary calciprotein particles (CPP2) and the speed of transformation (T50) from primary calciprotein particles (CPP1) to CPP2 in serum may be associated with vascular calcification (VC) in patients with chronic kidney disease (CKD). METHODS We developed a high throughput, microplate-based assay using dynamic light scattering (DLS) to measure the transformation of CPP1 to CPP2, hydrodynamic radius (Rh) of CPP1 and CPP2, T50 and aggregation of CPP2. We used this DLS assay to test the hypothesis that a large Rh of CPP2 and/or a fast T50 are associated with VC in 45 participants with CKD Stages 4-5 (22 without VC and 23 with VC) and 17 healthy volunteers (HV). VC was defined as a Kauppila score >6 or an Adragao score ≥3. RESULTS CKD participants with VC had larger cumulants Rh of CPP2 {370 nm [interquartile range (IQR) 272-566]} compared with CKD participants without VC [212 nm (IQR 169-315)] and compared with HV [168 nm (IQR 145-352), P < 0.01 for each]. More CPP2 were in aggregates in CKD participants with VC than those without VC (70% versus 36%). The odds of having VC increased by 9% with every 10 nm increase in the Rh of CPP2, after adjusting for age, diabetes, serum calcium and phosphate [odds ratio 1.09, 95% confidence interval (CI) 1.03, 1.16, P = 0.005]. The area under the receiver operating characteristic curve for VC of CPP2 size was 0.75 (95% CI 0.60, 0.90). T50 was similar in CKD participants with and without VC, although both groups had a lower T50 than HV. CONCLUSIONS Rh of CPP2, but not T50, is independently associated with VC in patients with CKD Stages 4-5.
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Affiliation(s)
- Wei Chen
- Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Viktoriya Anokhina
- Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Gregory Dieudonne
- Department of Radiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | | | - Randeep Kashyap
- Department of Surgery, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Chen Yan
- Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Tong Tong Wu
- Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Karen L de Mesy Bentley
- Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - Benjamin L Miller
- Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
- Department of Dermatology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
- Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
| | - David A Bushinsky
- Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
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12
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Shemies RS, Gaber TZ, Radwan ST, Mansour M, Mofreh M, Albehairy A, Bahriz R, Nagy E, Sayed Ahmed N, Nassar MK. Association between Plasma Dehydroepiandrosterone Sulfate and Carotid Intima-Media Thickness among Male and Female Patients with End-Stage Renal Disease on Hemodialysis. Cardiorenal Med 2019; 10:61-68. [PMID: 31770749 DOI: 10.1159/000504083] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Accepted: 10/08/2019] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND AND AIM Serum dehydroepiandrosterone sulfate (DHEA-S) is known to be lower in chronic kidney disease (CKD) patients and in those with cardiac disease, and correlates with a poor cardiovascular outcome. This study aimed to assess the correlation between DHEA-S and carotid intima-media thickness (CIMT) as a predictor of cardiovascular disease in hemodialysis (HD) patients. METHODS A total of 88 HD patients were included in this cross-sectional study. They included 53 male (group I) and 35 female patients (group II). In addition to conventional history taking, clinical examination, and routine laboratory investigations, serum DHEA-S and CIMT were measured for all patients. CIMT was measured using B-mode ultrasonography, and the mean of maximum CIMT was recorded. The 2 patient groups were further classified according to the level of DHEA-S. The correlation between serum DHEA-S and CIMT was studied. RESULTS In male patients, CIMT and age were significantly higher in the group with low DHEA-S level (p = 0.003 and 0.001, respectively), while there was no significant difference in both parameters in females. A higher percentage of HCV-positive patients is present in the male group with low DHEA-S level (p = 0.009). Serum DHEA-S is significantly negatively correlated with CIMT in males (p = 0.003) but not in females, and has a significant negative correlation to age in both genders (p = 0.001 and 0.04, respectively). CONCLUSION Endocrinal disturbance representing as lower serum DHEA-S is associated with increased CIMT, which is considered a predictor of cardiovascular disease in male HD patients, although it is largely explained by advancing age.
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Affiliation(s)
- Rasha Samir Shemies
- Department of Nephrology and Dialysis, Mansoura University, Mansoura, Egypt,
| | - Tamer Zaki Gaber
- Department of Nephrology and Dialysis, Mansoura University, Mansoura, Egypt
| | | | - Mostafa Mansour
- Department of Clinical Pathology, Mansoura University, Mansoura, Egypt
| | - Mohamed Mofreh
- Department of Clinical Pathology, Mansoura University, Mansoura, Egypt
| | - Ahmed Albehairy
- Department of Diabetes and Endocrinology, Mansoura University, Mansoura, Egypt
| | - Rania Bahriz
- Department of Diabetes and Endocrinology, Mansoura University, Mansoura, Egypt
| | - Eman Nagy
- Department of Nephrology and Dialysis, Mansoura University, Mansoura, Egypt
| | - Nagy Sayed Ahmed
- Department of Nephrology and Dialysis, Mansoura University, Mansoura, Egypt
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Smith ER, Hewitson TD, Holt SG. Diagnostic Tests for Vascular Calcification. Adv Chronic Kidney Dis 2019; 26:445-463. [PMID: 31831123 DOI: 10.1053/j.ackd.2019.07.001] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 07/22/2019] [Accepted: 07/28/2019] [Indexed: 02/06/2023]
Abstract
Vascular calcification (VC) is the heterogeneous endpoint of multiple vascular insults, which varies by arterial bed, the layer of the arterial wall affected, and is propagated by diverse cellular and biochemical mechanisms. A variety of in vivo and ex vivo techniques have been applied to the analysis of VC in preclinical studies, but clinical examination has principally relied on a number of noninvasive and invasive imaging modalities for detection and quantitation. Most imaging methods suffer from suboptimal spatial resolution, leading to the inability to distinguish medial from intimal VC and insufficient sensitivity to detect microcalcifications that are indicative of active mineral deposition and of vulnerable plaques which may be prone to rupture. Serum biomarkers lack specificity for VC and cannot discriminate pathology. Overall, uncertainties surrounding the sensitivity and specificity of different VC testing modalities, the absence of a clear cause-effect relationship, and lack of any evidence-based diagnostic or therapeutic protocols in relation to VC testing in chronic kidney disease has yielded weak or ungraded recommendations for their use in clinical practice. While VC is recognized as a key manifestation of chronic kidney disease-mineral and bone disorder and those with an increasing burden of VC are considered to be at higher cardiovascular risk, routine screening is not currently recommended.
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Valdivielso JM, Rodríguez-Puyol D, Pascual J, Barrios C, Bermúdez-López M, Sánchez-Niño MD, Pérez-Fernández M, Ortiz A. Atherosclerosis in Chronic Kidney Disease: More, Less, or Just Different? Arterioscler Thromb Vasc Biol 2019; 39:1938-1966. [PMID: 31412740 DOI: 10.1161/atvbaha.119.312705] [Citation(s) in RCA: 192] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Patients with chronic kidney disease (CKD) are at an increased risk of premature mortality, mainly from cardiovascular causes. The association between CKD on hemodialysis and accelerated atherosclerosis was described >40 years ago. However, more recently, it has been suggested that the increase in atherosclerosis risk is actually observed in early CKD stages, remaining stable thereafter. In this regard, interventions targeting the pathogenesis of atherosclerosis, such as statins, successful in the general population, have failed to benefit patients with very advanced CKD. This raises the issue of the relative contribution of atherosclerosis versus other forms of cardiovascular injury such as arteriosclerosis or myocardial injury to the increased cardiovascular risk in CKD. In this review, the pathophysiogical contributors to atherosclerosis in CKD that are shared with the general population, or specific to CKD, are discussed. The NEFRONA study (Observatorio Nacional de Atherosclerosis en NEFrologia) prospectively assessed the prevalence and progression of subclinical atherosclerosis (plaque in vascular ultrasound), confirming an increased prevalence of atherosclerosis in patients with moderate CKD. However, the adjusted odds ratio for subclinical atherosclerosis increased with CKD stage, suggesting a contribution of CKD itself to subclinical atherosclerosis. Progression of atherosclerosis was closely related to CKD progression as well as to the baseline presence of atheroma plaque, and to higher phosphate, uric acid, and ferritin and lower 25(OH) vitamin D levels. These insights may help design future clinical trials of stratified personalized medicine targeting atherosclerosis in patients with CKD. Future primary prevention trials should enroll patients with evidence of subclinical atherosclerosis and should provide a comprehensive control of all known risk factors in addition to testing any additional intervention or placebo.
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Affiliation(s)
- José M Valdivielso
- From the Vascular & Renal Translational Research Group and UDETMA, IRBLleida. Spanish Research Network for Renal Diseases (RedInRen. ISCIII), Lleida, Spain (J.M.V., M.B.-L.)
| | - Diego Rodríguez-Puyol
- Nephrology Unit, Fundación para la investigación del Hospital Universitario Príncipe de Asturias, RedInRen, Alcalá de Henares, Madrid, Spain (D.R.-P.)
| | - Julio Pascual
- Department of Nephrology, Institute Mar for Medical Research, Hospital del Mar, RedInRen, Barcelona, Spain (J.P., C.B.)
| | - Clara Barrios
- Department of Nephrology, Institute Mar for Medical Research, Hospital del Mar, RedInRen, Barcelona, Spain (J.P., C.B.)
| | - Marcelino Bermúdez-López
- From the Vascular & Renal Translational Research Group and UDETMA, IRBLleida. Spanish Research Network for Renal Diseases (RedInRen. ISCIII), Lleida, Spain (J.M.V., M.B.-L.)
| | - Maria Dolores Sánchez-Niño
- IIS-Fundacion Jimenez Diaz, School of Medicine, University Autonoma of Madrid, FRIAT and RedInRen, Madrid, Spain (M.D.S.-N., A.O.)
| | | | - Alberto Ortiz
- IIS-Fundacion Jimenez Diaz, School of Medicine, University Autonoma of Madrid, FRIAT and RedInRen, Madrid, Spain (M.D.S.-N., A.O.)
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15
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Kuswardhani RT, Wiradharma KG, Kandarini Y, Widiana GR, Martadiani ED. Factors associated with carotid intima-media thickness in patients on maintenance hemodialysis. Int J Gen Med 2018; 12:1-6. [PMID: 30588063 PMCID: PMC6304075 DOI: 10.2147/ijgm.s178276] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
PURPOSE The aim of this study was to analyze the association of the carotid intima-media thickness (CIMT) with various parameters in patients on maintenance hemodialysis (mHD). METHODS A cross-sectional study was conducted, enrolling 68 subjects (41 men, 27 women) on mHD in the Hemodialysis Unit, Sanglah Hospital, Denpasar, Indonesia. CIMT was measured with B-mode ultrasonography using a USG Sonoace 8000 and a 7.5 MHz linear transducer. RESULTS CIMT was higher in subjects with cardiovascular disease (CVD) compared with those without CVD (0.6494 vs 0.7288 mm; P=0.026), and in men compared with women (0.7056 vs 0.6141 mm; P=0.003). CIMT was correlated with age (R=0.607; P<0.001), plasma albumin (R=-0.291, P=0.016), serum phosphate (R=-0.294, P=0.015), calcium-phosphate product (R=-0.284, P=0.011), and plasma high-sensitivity C-reactive protein (R=0.279, P=0.030). However, after multiple linear regression testing, only age consistently had a role in determining the CIMT value (β=0.452, P<0.001). CONCLUSION Subjects with CVD have higher CIMT than those without CVD and men had higher CIMT than women. In addition, older age, higher high-sensitivity C-reactive protein, and lower albumin, phosphate, and calcium-phosphate product levels were correlated with higher CIMT. Age was the most important marker for CIMT in subjects on mHD.
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Affiliation(s)
- Ra Tuty Kuswardhani
- Division of Geriatric Medicine, Department of Internal Medicine, Faculty of Medicine, Udayana University, Sanglah Hospital, Denpasar, Indonesia,
| | - Ketut Gede Wiradharma
- Department of Internal Medicine, Sumbawa District Hospital, Sumbawa Besar, Indonesia
| | - Yenny Kandarini
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Udayana University, Sanglah Hospital, Denpasar, Indonesia
| | - Gde Raka Widiana
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Udayana University, Sanglah Hospital, Denpasar, Indonesia
| | - Elysanti Dwi Martadiani
- Department of Radiology, Faculty of Medicine, Udayana University, Sanglah Hospital, Denpasar, Indonesia
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16
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Andrews ES, Perrenoud L, Nowak KL, You Z, Pasch A, Chonchol M, Kendrick J, Jalal D. Examining the effects of uric acid-lowering on markers vascular of calcification and CKD-MBD; A post-hoc analysis of a randomized clinical trial. PLoS One 2018; 13:e0205831. [PMID: 30356327 PMCID: PMC6200237 DOI: 10.1371/journal.pone.0205831] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Accepted: 10/01/2018] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Chronic kidney disease (CKD)-mineral and bone disorder (MBD) is a systemic disorder that leads to vascular calcification and accelerated atherosclerosis. Uric acid has been shown to associate with vascular calcification and with carotid intima-media thickness (CIMT) and to suppress the 1 α-hydroxylase enzyme leading to lower 1,25-dihydroxyvitamin D (1,25(OH)2D) and higher intact parathyroid hormone (iPTH) levels. We hypothesized that lowering serum uric acid would reduce CIMT, calcification propensity, and circulating markers of CKD-MBD in CKD. METHODS This is a post-hoc analysis of a randomized, double-blind study of 80 patients with stage 3 CKD and hyperuricemia who received allopurinol or placebo for 12 weeks. CIMT and T50 were measured as markers of vascular disease and serum calcification propensity, respectively. The following markers of CKD-MBD were measured: serum calcium, phosphorus, vitamin D metabolites, iPTH, and fibroblast growth factor-23 (FGF-23). Expression of extra-renal 1α-hydroxylase was evaluated in endothelial cells of study participants. FINDINGS Allopurinol successfully lowered serum uric acid levels compared to placebo with an estimate of -3.3 mg/dL (95% C.I. -4.1,-2.5; p < 0.0001). After 12 weeks, however, we found no significant change in CIMT or serum T50. There was not a significant change in vitamin D metabolites, iPTH, FGF-23, or the expression of endothelial 1α-hydroxylase. CONCLUSION These data suggest that factors other than uric acid may play a more important role in the regulation of CKD- MBD including vascular calcification and vitamin D metabolism in patients with CKD.
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Affiliation(s)
- Emily S. Andrews
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Loni Perrenoud
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Kristen L. Nowak
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Zhiying You
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Andreas Pasch
- Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Michel Chonchol
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Jessica Kendrick
- Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Diana Jalal
- Nephrology Division, The University of Iowa, Iowa City, IA, United States of America
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17
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Mizuiri S, Nishizawa Y, Yamashita K, Mizuno K, Ishine M, Doi S, Masaki T, Shigemoto K. Coronary artery calcification score and common iliac artery calcification score in non-dialysis CKD patients. Nephrology (Carlton) 2018; 23:837-845. [PMID: 28703899 PMCID: PMC6120488 DOI: 10.1111/nep.13113] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/04/2017] [Indexed: 12/27/2022]
Abstract
AIM Many studies have validated Agatston's coronary artery calcification score (CACS) for assessing vascular calcification (VC) in chronic kidney disease (CKD) patients. This study aimed to evaluate the CACS and common iliac artery calcification score (IACS) and to examine the variables related to each score. METHODS The subjects were 145 non-dialysis CKD patients. The CACS and IACS were determined using the same thoracicoabdominal multi-detector computed tomography. Multiple regression analyses were performed to assess the factors associated with the CACS or IACS. The associations between progression to renal replacement therapy (RRT) and the CACS or IACS were studied using Cox hazards models. RESULTS The subjects' median age, estimated glomerular filtration rate (eGFR), and follow-up period were 72 (62-78) years, 32 (18-50) mL/min/1.73m2 , and 864 (550-1425) days, respectively. Age, diabetes, the serum phosphate level, and the eGFR were found to be significant factors of the CACS [β (95% CI): 0.38 (0.02-0.04), P < 0.0001, 0.28 (0.19-0.50), P < 0.0001, 0.16 (0.03-0.45), P < 0.05 and -0.15 (-0.02-0.00), P < 0.05, respectively]. Age and diabetes were shown to be significant factors of the IACS [β (95% CI): 0.53 (0.04-0.06), P < 0.0001, and 0.18 (0.07-0.40), P < 0.01, respectively]. Progression to RRT occurred in 31 patients and was significantly associated with the CACS (hazard ratio: 1.01, P < 0.01), urinary protein level and eGFR, but not the IACS. CONCLUSION Chronic kidney disease related risk factors for VC, such as the eGFR and hyperphosphataemia, are significantly associated with a high CACS, but not a high IACS, and the CACS is a significant predictor of progression to RRT.
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Affiliation(s)
- Sonoo Mizuiri
- Department of NephrologyIchiyokai Harada HospitalHiroshimaJapan
| | | | | | - Kenji Mizuno
- Department of RadiologyIchiyokai Harada HospitalHiroshimaJapan
| | - Masahiro Ishine
- Department of RadiologyIchiyokai Harada HospitalHiroshimaJapan
| | - Shigehiro Doi
- Department of NephrologyHiroshima University HospitalHiroshimaJapan
| | - Takao Masaki
- Department of NephrologyHiroshima University HospitalHiroshimaJapan
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18
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Palanca A, Castelblanco E, Perpiñán H, Betriu À, Soldevila B, Valdivielso JM, Bermúdez M, Duran X, Fernández E, Puig-Domingo M, Groop PH, Alonso N, Mauricio D. Prevalence and progression of subclinical atherosclerosis in patients with chronic kidney disease and diabetes. Atherosclerosis 2018; 276:50-57. [PMID: 30032025 DOI: 10.1016/j.atherosclerosis.2018.07.018] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Revised: 06/21/2018] [Accepted: 07/12/2018] [Indexed: 10/28/2022]
Abstract
BACKGROUND AND AIMS Cardiovascular disease is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD) and diabetes. Traditional cardiovascular risk factors fail to fully account for the increase in cardiovascular risk in these patients. This study aims to analyse the prevalence and progression of subclinical atherosclerosis in CKD patients with and without diabetes. METHODS We included data from CKD patients with and without diabetes free from previous cardiovascular events from the NEFRONA cohort. Patients underwent baseline and 24-month follow-up carotid and femoral ultrasound examinations. Multivariable models were used to assess the contribution of diabetes to the presence and plaque progression. RESULTS A total of 419 patients with diabetes and 1129 without diabetes were included. Diabetic patients were older, had higher BMIs, more hypertension and dyslipidaemia. At baseline, the proportion of patients with plaque was higher among diabetic patients (81.4% vs. 64.1%, p < 0.001). Diabetic patients more frequently had more than two vascular territories with plaque (64.4% vs. 48.4%, p < 0.001). Multivariable analysis indicated that plaque at baseline was significantly associated with age, gender, smoking and renal replacement therapy (RRT) in the non-diabetic patients, but only with age and male gender in diabetic patients. Plaque progression was significantly associated with age, number of territories with basal plaque, smoking and RRT in both groups. CONCLUSIONS Subclinical atherosclerosis is more prevalent, carries a higher plaque burden and is more rapidly progressive in renal patients with diabetes. In these patients, diabetes outweighs other described risk factors associated with the presence of subclinical atherosclerosis.
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Affiliation(s)
- Ana Palanca
- Department of Endocrinology and Nutrition, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Barcelona Autonomous University (UAB), Barcelona, Spain
| | - Esmeralda Castelblanco
- Department of Endocrinology and Nutrition, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain; Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
| | - Hèctor Perpiñán
- Biostatistics Unit, Institut de Recerca Biomèdica de Lleida, Spain
| | - Àngels Betriu
- Vascular and Renal Translational Research Group. Institut de Recerca Biomèdica de Lleida, Spain
| | - Berta Soldevila
- Department of Endocrinology and Nutrition, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Barcelona Autonomous University (UAB), Barcelona, Spain; Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
| | - José Manuel Valdivielso
- Vascular and Renal Translational Research Group. Institut de Recerca Biomèdica de Lleida, Spain
| | - Marcelino Bermúdez
- Vascular and Renal Translational Research Group. Institut de Recerca Biomèdica de Lleida, Spain
| | - Xavier Duran
- Methodological and Biostatistical Advisory Service, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain
| | - Elvira Fernández
- Vascular and Renal Translational Research Group. Institut de Recerca Biomèdica de Lleida, Spain
| | - Manel Puig-Domingo
- Department of Endocrinology and Nutrition, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Barcelona Autonomous University (UAB), Barcelona, Spain; Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain
| | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland; Abdominal Center Nephrology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland; Baker IDI Heart and Diabetes Institute, Melbourne, Australia
| | - Núria Alonso
- Department of Endocrinology and Nutrition, Health Sciences Research Institute & University Hospital Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Barcelona Autonomous University (UAB), Barcelona, Spain; Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain.
| | - Dídac Mauricio
- Department of Medicine, Barcelona Autonomous University (UAB), Barcelona, Spain; Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Spain; Department of Endocrinology and Nutrition, University Hospital de la Santa Creu i Sant Pau & Institut d'Investigació Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain.
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Valdivielso JM, Bozic M, Galimudi RK, Bermudez-López M, Navarro-González JF, Fernández E, Betriu À. Association of the rs495392 Klotho polymorphism with atheromatosis progression in patients with chronic kidney disease. Nephrol Dial Transplant 2018; 34:2079-2088. [DOI: 10.1093/ndt/gfy207] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 06/04/2018] [Indexed: 02/07/2023] Open
Abstract
Abstract
Background
Prevalence of atherosclerotic cardiovascular disease and its rate of progression are higher in patients with chronic kidney disease (CKD) compared with the general population. Mineral metabolism parameters have been shown to be involved in the increased velocity of atheromatosis progression. The aim of this study is to determine the role of 11 single-nucleotide polymorphisms (SNPs) of the Klotho gene on the rate of atherosclerosis progression in CKD.
Methods
This was a multicentre, prospective, observational study of 1439 CKD patients from the NEFRONA cohort. Carotid and femoral ultrasounds were performed at baseline and after 24 months in 10 arterial territories. Progression of atheromatosis was defined as an increase in the number of territories with plaque. Genotyping of 11 SNPs of the Klotho gene was performed and its association with atheromatosis progression was determined by multivariate logistic regression.
Results
Bivariate analysis showed that none of the 11 SNPs was associated with atheroma plaque prevalence, but 3 of them (rs495392, rs562020 and rs567170) showed association with atheromatosis progression. The multivariate analysis revealed that only rs495392 showed a statistically significant association with atheromatosis progression, after adjustment for several parameters known to affect it in CKD patients. Thus, the presence of one allele T was associated with a reduction of 30% of the odds of progression, whereas the presence of the two T alleles was associated with a decrease close to 50%.
Conclusions
The presence of the allele T of the SNP rs495392 of the Klotho gene is associated with a decrease in the odds of progression of atheromatosis in CKD patients.
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Affiliation(s)
- José M Valdivielso
- Vascular and Renal Translational Research Group, Biomedical Research Institute, IRBLleida, RedinRen RETIC, ISCIII, Lleida, Spain
| | - Milica Bozic
- Vascular and Renal Translational Research Group, Biomedical Research Institute, IRBLleida, RedinRen RETIC, ISCIII, Lleida, Spain
| | - Rajesh Kumar Galimudi
- Vascular and Renal Translational Research Group, Biomedical Research Institute, IRBLleida, RedinRen RETIC, ISCIII, Lleida, Spain
| | - Marcelino Bermudez-López
- Vascular and Renal Translational Research Group, Biomedical Research Institute, IRBLleida, RedinRen RETIC, ISCIII, Lleida, Spain
| | - Juan F Navarro-González
- Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain
| | - Elvira Fernández
- Department of Nephrology, University Hospital Arnau de Vilanova, Lleida, Spain
| | - Àngels Betriu
- Vascular and Renal Translational Research Group, Biomedical Research Institute, IRBLleida, RedinRen RETIC, ISCIII, Lleida, Spain
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Bozic M, Betriu A, Bermudez-Lopez M, Ortiz A, Fernandez E, Valdivielso JM. Association of FGF-2 Concentrations with Atheroma Progression in Chronic Kidney Disease Patients. Clin J Am Soc Nephrol 2018; 13:577-584. [PMID: 29519952 PMCID: PMC5969461 DOI: 10.2215/cjn.07980717] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Accepted: 01/03/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND AND OBJECTIVES Atherosclerosis is highly prevalent in CKD. The rate of progression of atherosclerosis is associated with cardiovascular events. Fibroblast growth factor 2 (FGF-2) is a member of the FGF family with potentially both protective and deleterious effects in the development of atherosclerosis. The role of circulating FGF-2 levels in the progression of atherosclerosis in CKD is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We used a multicenter, prospective, observational cohorts study of 481 patients with CKD. We determined the presence of atheroma plaque in ten arterial territories by carotid and femoral ultrasounds. Progression of atheromatosis was defined as an increase in the number of territories with plaque after 24 months. Plasma levels of FGF-2 were measured by multiplex analysis. A multivariable logistic regression analysis was performed to determine whether plasma FGF-2 levels were associated with atheromatosis progression. RESULTS Average age of the population was 61 years. The percentage of patients in each CKD stage was 51% in stage 3, 41% in stages 4-5, and 8% in dialysis. A total of 335 patients (70%) showed plaque at baseline. Atheromatosis progressed in 289 patients (67%). FGF-2 levels were similar between patients with or without plaque at baseline (79 versus 88 pg/ml), but lower in patients with atheromatosis progression after 2 years (78 versus 98 pg/ml; P<0.01). In adjusted analyses, higher plasma FGF-2 was associated with lower risk of atheromatosis progression (odds ratio [OR], 0.86; 95% confidence interval [95% CI], 0.76 to 0.96; per 50 pg/ml increment). Analysis of FGF-2 in tertiles showed that atheroma progression was observed for 102 participants in the lowest tertile of FGF-2 (reference group), 86 participants in the middle tertile of FGF-2 (adjusted OR, 0.70; 95% CI, 0.40 to 1.20), and 74 participants in the lowest tertile of FGF-2 (adjusted OR, 0.48; 95% CI, 0.28 to 0.82). CONCLUSIONS Low FGF-2 levels are independently associated with atheromatosis progression in CKD.
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Affiliation(s)
- Milica Bozic
- Vascular and Renal Translational Research Group, Institut de Recerca Biomedica de Lleida, Lleida, Spain; and
| | - Angels Betriu
- Vascular and Renal Translational Research Group, Institut de Recerca Biomedica de Lleida, Lleida, Spain; and
| | - Marcelino Bermudez-Lopez
- Vascular and Renal Translational Research Group, Institut de Recerca Biomedica de Lleida, Lleida, Spain; and
| | - Alberto Ortiz
- Instituto de Investigacion Sanitaria Fundación Jiménez Díaz, Autonomous University of Madrid, Red de Investigación Renal del Instituto de Salud Carlos III, Madrid, Spain
| | - Elvira Fernandez
- Vascular and Renal Translational Research Group, Institut de Recerca Biomedica de Lleida, Lleida, Spain; and
| | - Jose M. Valdivielso
- Vascular and Renal Translational Research Group, Institut de Recerca Biomedica de Lleida, Lleida, Spain; and
| | - on behalf of the NEFRONA investigators
- Vascular and Renal Translational Research Group, Institut de Recerca Biomedica de Lleida, Lleida, Spain; and
- Instituto de Investigacion Sanitaria Fundación Jiménez Díaz, Autonomous University of Madrid, Red de Investigación Renal del Instituto de Salud Carlos III, Madrid, Spain
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Valdivielso JM, Betriu A, Martinez-Alonso M, Arroyo D, Bermudez-Lopez M, Fernandez E. Factors predicting cardiovascular events in chronic kidney disease patients. Role of subclinical atheromatosis extent assessed by vascular ultrasound. PLoS One 2017; 12:e0186665. [PMID: 29045466 PMCID: PMC5646852 DOI: 10.1371/journal.pone.0186665] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Accepted: 10/05/2017] [Indexed: 01/12/2023] Open
Abstract
Patients with chronic kidney disease (CKD) have an increased incidence of cardiovascular events (CVE). The contribution of subclinical atheromatosis extent, including femoral arteries, to CVE in CKD patients has not been investigated. In this paper, we examine the prognostic value of subclinical atheromatosis extent, assessed as the number of arterial territories with plaque, in predicting the incidence of major and minor CVE. The NEFRONA is a multicenter, prospective cohorts study that recruited 2445 CKD subjects and 559 controls, free from previous cardiovascular disease, in 81 medical centers across Spain. The presence of atheroma plaque was assessed by arterial ultrasound in ten arterial territories (carotid and femoral). The predictive power of the presence or absence of atheroma plaque in any territory was compared with the quantification of atheroma extent as the number of territories with plaque. During the median follow up of 48 months, 216 CVE were reported. Factors predicting the incidence of CVE in the whole cohort were being male, CKD patient, lower levels of 25(OH) vitamin D, higher levels of cholesterol and the extent of subclinical atheromatosis, yielding a higher concordance (C) index than the presence or absence of plaque. In stratified analysis including specific factors of CKD patients not on dialysis, the variables predicting CVE were the same as in the whole cohort, plus higher levels of potassium. Again, the inclusion of the information about atheromatosis as number of territories with plaque, presented a higher C index than the presence or absence of plaque. In the dialysis population, significant variables were older age, diabetes, dialysis vintage and higher levels of cholesterol and phosphate. In this case the higher C index was obtained with the information about plaque presence. Subclinical atheromatosis extent, including femoral arteries, influences CVE in CKD and its detection could improve the prediction of cardiovascular events.
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Affiliation(s)
- José M. Valdivielso
- Vascular and Renal Translational Research Group, UDETMA, REDinREN del ISCIII, IRBLleida, Lleida, Spain
- * E-mail: (JMV); (EF)
| | - Angels Betriu
- Vascular and Renal Translational Research Group, UDETMA, REDinREN del ISCIII, IRBLleida, Lleida, Spain
| | | | - David Arroyo
- Vascular and Renal Translational Research Group, UDETMA, REDinREN del ISCIII, IRBLleida, Lleida, Spain
| | - Marcelino Bermudez-Lopez
- Vascular and Renal Translational Research Group, UDETMA, REDinREN del ISCIII, IRBLleida, Lleida, Spain
| | - Elvira Fernandez
- Vascular and Renal Translational Research Group, UDETMA, REDinREN del ISCIII, IRBLleida, Lleida, Spain
- * E-mail: (JMV); (EF)
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Rroji M, Spahia N, Seferi S, Barbullushi M, Spasovski G. Influence of Residual Renal Function in Carotid Modeling as a Marker of Early Atherosclerosis in Dialysis Patients. Ther Apher Dial 2017; 21:451-458. [PMID: 28714271 DOI: 10.1111/1744-9987.12548] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Revised: 01/19/2017] [Indexed: 11/27/2022]
Abstract
Atherosclerosis is frequently present in patients with chronic kidney disease (CKD) treated with dialysis. We evaluated the association between residual renal function (RRF), phosphate level, inflammation and other risk factors in carotid modeling as a marker of early atherosclerosis in peritoneal dialysis (PD) compared with hemodialysis (HD) patients. We studied 39 stable PD and 53 HD patients on renal replacement therapy (RRT) for 3 to 36 months duration. B-mode ultrasonography was used to determine carotid artery intima media thickness (CIMT). We classified patients with atherosclerosis if they have CIMT >10 mm and or presence of plaque. Out of our total dialysis population studied of 92 patients, 16.3% were diabetics and 57.6% were on hemodialysis. Expectedly, PD patients had a higher RRF (P < 0.001), 24 h urine volume (P < 0.001); C-reactive protein (P = 0.047), and a lower serum phosphate (P = 0.01), PTH (P < 0.05), alkaline phosphatase (P < 0.05), and albumin levels (P < 0.001) compared to hemodialysis patients. Atherosclerosis was found in 66.3% of patients and in 100% of a diabetic population. There was no significant difference in the presence of atherosclerosis between PD and HD patients [56.4 vs 73.6% HD, respectively]. Multiple regression analysis showed age, diabetes, HD modality, RRF, phosphate, PTH and pulse pressure as independent parameters associated with atherosclerosis. Apart from the traditional risk factors like age and diabetes, our study showed a link of atherosclerosis with metabolic abnormalities secondary to renal failure. We demonstrated a novel, independent association between RRF and atherosclerosis, underlining the importance of preservation of the RRF in dialysis patients.
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Affiliation(s)
- Merita Rroji
- Department of Nephrology-Dialysis, UHC "Mother Teresa", Tirana, Albania
| | - Nereida Spahia
- Department of Nephrology-Dialysis, UHC "Mother Teresa", Tirana, Albania
| | - Saimir Seferi
- Department of Nephrology-Dialysis, UHC "Mother Teresa", Tirana, Albania
| | | | - Goce Spasovski
- University Department of Nephrology, Medical Faculty, University of Skopje, Skopje, Macedonia
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Disthabanchong S, Boongird S. Role of different imaging modalities of vascular calcification in predicting outcomes in chronic kidney disease. World J Nephrol 2017; 6:100-110. [PMID: 28540199 PMCID: PMC5424431 DOI: 10.5527/wjn.v6.i3.100] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 03/27/2017] [Accepted: 04/19/2017] [Indexed: 02/06/2023] Open
Abstract
Vascular calcification (VC) is common among patients with chronic kidney disease (CKD). The severity of VC is associated with increased risk of cardiovascular events and mortality. Risk factors for VC include traditional cardiovascular risk factors as well as CKD-related risk factors such as increased calcium and phosphate load. VC is observed in arteries of all sizes from small arterioles to aorta, both in the intima and the media of arterial wall. Several imaging techniques have been utilized in the evaluation of the extent and the severity of VC. Plain radiographs are simple and readily available but with the limitation of decreased sensitivity and subjective and semi-quantitative quantification methods. Mammography, especially useful among women, offers a unique way to study breast arterial calcification, which is largely a medial-type calcification. Ultrasonography is suitable for calcification in superficial arteries. Analyses of wall thickness and lumen size are also possible. Computed tomography (CT) scan, the gold standard, is the most sensitive technique for evaluation of VC. CT scan of coronary artery calcification is not only useful for cardiovascular risk stratification but also offers an accurate and an objective analysis of the severity and progression.
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24
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Abstract
BACKGROUND Subjects with type 2 diabetes mellitus are considered to be at high risk for cardiovascular disease. The identification of carotid atherosclerosis is a validated surrogate marker of cardiovascular disease. Nurses are key professionals in the improvement and intensification of cardiovascular preventive strategies. AIMS The aim is to study the presence of carotid atherosclerosis in a group of asymptomatic subjects with type 2 diabetes mellitus and no previous clinical cardiovascular disease. METHODS A total of 187 patients with type 2 diabetes mellitus and 187 age- and sex-matched subjects without type 2 diabetes mellitus were studied in this cross-sectional, observational, cohort study. Standard operational procedures were applied by the nursing team regarding physical examination and carotid ultrasound assessment. Common, bulb, and internal carotid arteries were explored by measuring intima-media thickness and identifying atherosclerotic plaques. RESULTS Carotid intima-media thickness (c-IMT) and carotid plaque prevalence were significantly greater in diabetic subjects than in the control group. Carotid plaques and c-IMT were more frequent in men than in women and increased with increasing age. In the multivariate analysis, age, gender, waist circumference, systolic blood pressure, and hypercholesterolemia were positively associated with c-IMT, whereas age, gender, and weight were positively associated with carotid plaque. CONCLUSION The current nurse-led study shows that subjects with type 2 diabetes mellitus have a high prevalence of subclinical atherosclerosis that is associated with cardiovascular risk factors.
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Bover J, Górriz JL, Ureña-Torres P, Lloret MJ, Ruiz-García C, daSilva I, Chang P, Rodríguez M, Ballarín J. Detección de las calcificaciones cardiovasculares: ¿una herramienta útil para el nefrólogo? Nefrologia 2016; 36:587-596. [DOI: 10.1016/j.nefro.2016.05.021] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 05/19/2016] [Indexed: 12/12/2022] Open
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Bover J, Ureña-Torres P, Górriz JL, Lloret MJ, da Silva I, Ruiz-García C, Chang P, Rodríguez M, Ballarín J. Cardiovascular calcifications in chronic kidney disease: Potential therapeutic implications. Nefrologia 2016; 36:597-608. [PMID: 27595517 DOI: 10.1016/j.nefro.2016.05.023] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2016] [Accepted: 05/19/2016] [Indexed: 02/06/2023] Open
Abstract
Cardiovascular (CV) calcification is a highly prevalent condition at all stages of chronic kidney disease (CKD) and is directly associated with increased CV and global morbidity and mortality. In the first part of this review, we have shown that CV calcifications represent an important part of the CKD-MBD complex and are a superior predictor of clinical outcomes in our patients. However, it is also necessary to demonstrate that CV calcification is a modifiable risk factor including the possibility of decreasing (or at least not aggravating) its progression with iatrogenic manoeuvres. Although, strictly speaking, only circumstantial evidence is available, it is known that certain drugs may modify the progression of CV calcifications, even though a direct causal link with improved survival has not been demonstrated. For example, non-calcium-based phosphate binders demonstrated the ability to attenuate the progression of CV calcification compared with the liberal use of calcium-based phosphate binders in several randomised clinical trials. Moreover, although only in experimental conditions, selective activators of the vitamin D receptor seem to have a wider therapeutic margin against CV calcification. Finally, calcimimetics seem to attenuate the progression of CV calcification in dialysis patients. While new therapeutic strategies are being developed (i.e. vitamin K, SNF472, etc.), we suggest that the evaluation of CV calcifications could be a diagnostic tool used by nephrologists to personalise their therapeutic decisions.
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Affiliation(s)
- Jordi Bover
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España.
| | - Pablo Ureña-Torres
- Departamento de Nefrología y Diálisis, Clinique du Landy, París, Francia; Departamento de Fisiología Renal, Hospital Necker, Universidad de París Descartes, París, Francia
| | - José Luis Górriz
- Servicio de Nefrología, Hospital Universitario Dr. Peset, Valencia, España
| | - María Jesús Lloret
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España
| | - Iara da Silva
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España
| | - César Ruiz-García
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España
| | - Pamela Chang
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España
| | - Mariano Rodríguez
- Servicio de Nefrología, Hospital Universitario Reina Sofía, IMIBIC, Universidad de Córdoba, Córdoba, España
| | - José Ballarín
- Servicio de Nefrología, Fundació Puigvert, IIB Sant Pau, RedinRen, Barcelona, España
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Gracia M, Betriu À, Martínez-Alonso M, Arroyo D, Abajo M, Fernández E, Valdivielso JM. Predictors of Subclinical Atheromatosis Progression over 2 Years in Patients with Different Stages of CKD. Clin J Am Soc Nephrol 2015; 11:287-96. [PMID: 26668022 DOI: 10.2215/cjn.01240215] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2015] [Accepted: 11/02/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND OBJECTIVES Ultrasonographic detection of subclinical atheromatosis is a noninvasive method predicting cardiovascular events. Risk factors predicting atheromatosis progression in CKD are unknown. Predictors of atheromatosis progression were evaluated in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Our multicenter, prospective, observational study included 1553 patients with CKD (2009-2011). Carotid and femoral ultrasounds were performed at baseline and after 24 months. A subgroup of 476 patients with CKD was also randomized to undergo ultrasound examination at 12 months. Progression of atheromatosis was defined as an increase in the number of plaque territories analyzed by multivariate logistic regression. RESULTS Prevalence of atheromatosis was 68.7% and progressed in 59.8% of patients after 24 months. CKD progression was associated with atheromatosis progression, suggesting a close association between pathologies. Variables significantly predicting atheromatosis progression, independent from CKD stages, were diabetes and two interactions of age with ferritin and plaque at baseline. Given that multiple interactions were found between CKD stage and age, phosphate, smoking, dyslipidemia, body mass index, systolic BP (SBP), carotid intima-media thickness, plaque at baseline, uric acid, cholesterol, 25-hydroxy vitamin D (25OH vitamin D), and antiplatelet and phosphate binders use, the analysis was stratified by CKD stages. In stage 3, two interactions (age with phosphate and plaque at baseline) were found, and smoking, diabetes, SBP, low levels of 25OH vitamin D, and no treatment with phosphate binders were positively associated with atheromatosis progression. In stages 4 and 5, three interactions (age with ferritin and plaque and plaque with smoking) were found, and SBP was positively associated with atheromatosis progression. In dialysis, an interaction between body mass index and 25OH vitamin D was found, and age, dyslipidemia, carotid intima-media thickness, low cholesterol, ferritin, and uric acid were positively associated with atheromatosis progression. CONCLUSIONS Atheromatosis progression affects more than one half of patients with CKD, and predictive factors differ depending on CKD stage.
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Affiliation(s)
- Marta Gracia
- Experimental Nephrology, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain
| | - Àngels Betriu
- Experimental Nephrology, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain
| | | | - David Arroyo
- Nephrology, University Hospital Arnau de Vilanova, Lleida, Spain
| | - María Abajo
- Experimental Nephrology, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain
| | | | - José M Valdivielso
- Experimental Nephrology, Biomedical Research Institute of Lleida (IRBLleida), Lleida, Spain;
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Azancot MA, Ramos N, Torres IB, García-Carro C, Romero K, Espinel E, Moreso F, Seron D. Inflammation and Atherosclerosis Are Associated With Hypertension in Kidney Transplant Recipients. J Clin Hypertens (Greenwich) 2015; 17:963-9. [PMID: 26293391 PMCID: PMC8032044 DOI: 10.1111/jch.12634] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2015] [Revised: 04/14/2015] [Accepted: 04/15/2015] [Indexed: 11/27/2022]
Abstract
The aim of the current study was to evaluate risk factors associated with hypertension in kidney transplant recipients. The authors recruited 92 consecutive kidney transplant recipients and 30 age-matched patients with chronic kidney disease without history of cardiovascular events. Twenty-four-hour ambulatory blood pressure monitoring, pulse wave velocity, and carotid ultrasound were performed. Serum levels of log-transformed interleukin 6 (Log IL-6), soluble tumor necrosis factor receptor 2, and intercellular adhesion molecule 1 were determined. Twenty-four-hour systolic blood pressure (SBP) (P=.0001), Log IL-6 (P=.011), and total number of carotid plaques (P=.013) were higher, while the percentage decline of SBP from day to night was lower in kidney transplant recipients (P=.003). Independent predictors of 24-hour SBP were urinary protein/creatinine ratio and circulating monocytes (P=.001), while Log IL-6, serum creatinine, and total number of carotid plaques (P=.0001) were independent predictors of percentage decline of SBP from day to night. These results suggest that subclinical atherosclerosis and systemic inflammation are associated with hypertension after transplantation.
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Affiliation(s)
- Maria A Azancot
- Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Natalia Ramos
- Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Irina B Torres
- Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Clara García-Carro
- Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Katheryne Romero
- Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Eugenia Espinel
- Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Francesc Moreso
- Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Daniel Seron
- Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
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Hénaut L, Sanchez-Nino MD, Aldamiz-Echevarría Castillo G, Sanz AB, Ortiz A. Targeting local vascular and systemic consequences of inflammation on vascular and cardiac valve calcification. Expert Opin Ther Targets 2015; 20:89-105. [PMID: 26788590 DOI: 10.1517/14728222.2015.1081685] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION Cardiac valve calcification and vascular calcification (VC) are associated with cardiovascular mortality in the general population and in patients with chronic kidney disease (CKD). CKD, diabetes mellitus, and atherosclerosis are among the causes of systemic inflammation that are associated with VC. AREAS COVERED This review collates clinical and experimental evidence that inflammation accelerates VC progression. Specifically, we review the actions of key pro-inflammatory cytokines and inflammation-related transcription factors on VC, and the role played by senescence. Inflammatory cytokines, such as the TNF superfamily and IL-6 superfamily, and inflammation-related transcription factor NF-κB promote calcification in cultured vascular smooth muscle cells, valvular interstitial cells, or experimental animal models through direct effects, but also indirectly by decreasing circulating Fetuin A or Klotho levels. EXPERT OPINION Experimental evidence suggests a causal link between inflammation and VC that would change the clinical approach to prevention and treatment of VC. However, the molecular basis remains unclear and little is known about VC in humans treated with drugs targeting inflammatory cytokines. The effect of biologicals targeting TNF-α, RANKL, IL-6, and other inflammatory mediators on VC, in addition to the impact of dietary phosphate in patients with chronic systemic inflammation, requires study.
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Affiliation(s)
- Lucie Hénaut
- a 1 Universidad Autónoma de Madrid, School of Medicine, Nephrology, IIS-Fundación Jiménez Díaz , Madrid, Spain
| | - Maria Dolores Sanchez-Nino
- b 2Universidad Autónoma de Madrid, School of Medicine, IIS-Fundación Jiménez Díaz, Madrid, Spain.,c 3 REDINREN , Madrid, Spain
| | | | - Ana B Sanz
- b 2Universidad Autónoma de Madrid, School of Medicine, IIS-Fundación Jiménez Díaz, Madrid, Spain.,c 3 REDINREN , Madrid, Spain
| | - Alberto Ortiz
- c 3 REDINREN , Madrid, Spain.,e 5 Chief of nephrology, Universidad Autónoma de Madrid, School of Medicine, IIS-Fundación Jiménez Díaz , Madrid, Spain .,f 6 Fundación Renal Iñigo Alvarez de Toledo-IRSIN , Madrid, Spain
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Hernández D, Triñanes J, Salido E, Pitti S, Rufino M, González-Posada JM, Torres A. Artery Wall Assessment Helps Predict Kidney Transplant Outcome. PLoS One 2015; 10:e0129083. [PMID: 26066045 PMCID: PMC4466324 DOI: 10.1371/journal.pone.0129083] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 05/05/2015] [Indexed: 12/13/2022] Open
Abstract
Background Kidney transplant recipients have high cardiovascular risk, and vascular inflammation may play an important role. We explored whether the inflammatory state in the vessel wall was related to carotid intima-media thickness (c-IMT) and patient survival following kidney transplantation. Methods In this prospective observational cohort study we measured c-IMT and expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery in 115 kidney transplant candidates. Another c-IMT measurement was done 1-year post-transplantation in 107. By stepwise multiple regression analysis we explored factors associated with baseline c-IMT and their changes over time. Multivariate Cox regression analysis was constructed to identify risk factors for mortality. Results A worse cardiovascular profile (older age, smoker, diabetic, carotid plaque, systolic blood pressure and vascular calcification) and higher VCAM-1 levels were found in patients in the highest baseline c-IMT tertile, who also had a worse survival. Factors independently related to baseline c-IMT were age (β=0.369, P<0.0001), fasting glucose (β=0.168, P=0.045), smoking (β=0.228, P=0.003) and VCAM-1 levels (β=0.244, P=0.002). Independent factors associated with c-IMT measurement 1-year post-transplantation were baseline c-IMT (β=-0.677, P<0.0001), post-transplant diabetes (β=0.225, P=0.003) and triglycerides (β=0.302, P=0.023). Vascular VCAM-1 levels were associated with increased risk of mortality in bivariate and multivariate Cox regression. Notably, nearly 50% of patients showed an increase or maintenance of high c-IMT 1 year post-transplantation and these patients experienced a higher mortality (13 versus 3.5%; P=0.021). Conclusion A worse cardiovascular profile and a higher vascular VCAM-1 protein levels at time of KT are related to subclinical atheromatosis. This could lead to a higher post-transplant mortality. Pre-transplant c IMT, post-transplant diabetes and triglycerides at 1-year post-transplantation may condition a high c-IMT measurement post-transplantation, which may decrease patient survival.
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Affiliation(s)
- Domingo Hernández
- Nephrology Department, Carlos Haya Regional University Hospital and University of Málaga (IBIMA), REDinREN, Málaga, Spain
- * E-mail:
| | - Javier Triñanes
- Research Unit, Hospital Universitario de Canarias, Tenerife, Spain
| | - Eduardo Salido
- Research Unit, Hospital Universitario de Canarias, Tenerife, Spain
| | - Sergio Pitti
- Radiology Department, Hospital Universitario de Canarias, Tenerife, Spain
| | - Margarita Rufino
- Nephrology Department, Hospital Universitario de Canarias, CIBICAN, University of La Laguna, Instituto Reina Sofía de Investigación Renal (IRSIN), Tenerife, Spain
| | - José Manuel González-Posada
- Nephrology Department, Hospital Universitario de Canarias, CIBICAN, University of La Laguna, Instituto Reina Sofía de Investigación Renal (IRSIN), Tenerife, Spain
| | - Armando Torres
- Nephrology Department, Hospital Universitario de Canarias, CIBICAN, University of La Laguna, Instituto Reina Sofía de Investigación Renal (IRSIN), Tenerife, Spain
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Cardiovascular risk in chronic kidney disease patients: intima-media thickness predicts the incidence and severity of histologically assessed medial calcification in radial arteries. BMC Nephrol 2015; 16:78. [PMID: 26037625 PMCID: PMC4453281 DOI: 10.1186/s12882-015-0067-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2015] [Accepted: 05/20/2015] [Indexed: 11/24/2022] Open
Abstract
Background The objective of the study was to determine the relationship between common carotid artery intima-media thickness (CCA-IMT) and histologically assessed calcification of radial artery in relation to clinical features and laboratory markers of bone and mineral metabolism, inflammation, and oxidative stress in patients with stage 5 chronic kidney disease (CKD). Methods The study comprised 59 patients (36 hemodialyzed, 23 predialysis). CCA-IMT was measured by ultrasonography; the biochemical parameters examined were assessed using routine laboratory methods, ELISA micro-plate immunoassays and spectrophotometry. Fragments of radial artery obtained during creation of hemodialysis access were cryosectioned and stained for calcifications using von Kossa method and alizarin red. Results Glucose, osteoprotegerin, pentraxin 3 and Framingham risk score significantly correlated with CCA-IMT. In multiple regression analysis, OPG positively predicted CCA-IMT. Radial artery calcifications were found in 34 patients who showed higher CCA-IMT (0.98 ± 0.13 vs 0.86 ± 0.14 mm; P = 0.006). Higher CCA-IMT values were also associated with more advanced calcifications. CCA-IMT and the presence of plaques in common carotid artery were positive predictors of radial artery calcifications, independent of dialysis status, Framingham risk score, CRP and Ca x Pi [OR for calcifications 2.19 (1.08-4.45) per 0.1 mm increase in CCA-IMT]. The presence of radial artery calcifications was a significant predictor of mortality, independent of dialysis status and Framingham risk score [HR 3.16 (1.03-9.64)]. Conclusions In CKD patients, CCA-IMT examination can be used as a surrogate measure to assess the incidence and severity of arterial medial calcification which is associated with poor clinical outcome in these patients.
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Clinical Significance of Preexisting Microcalcification in the Iliac Artery in Renal Transplant Recipients. Transplantation 2015; 99:811-7. [DOI: 10.1097/tp.0000000000000409] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Chen W, Melamed ML. Vascular calcification in predialysis CKD: common and deadly. Clin J Am Soc Nephrol 2015; 10:551-3. [PMID: 25770177 DOI: 10.2215/cjn.01940215] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Wei Chen
- Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York; and
| | - Michal L Melamed
- Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
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Górriz JL, Molina P, Cerverón MJ, Vila R, Bover J, Nieto J, Barril G, Martínez-Castelao A, Fernández E, Escudero V, Piñera C, Adragao T, Navarro-Gonzalez JF, Molinero LM, Castro-Alonso C, Pallardó LM, Jamal SA. Vascular calcification in patients with nondialysis CKD over 3 years. Clin J Am Soc Nephrol 2015; 10:654-66. [PMID: 25770175 DOI: 10.2215/cjn.07450714] [Citation(s) in RCA: 140] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Accepted: 12/16/2014] [Indexed: 01/03/2023]
Abstract
BACKGROUND AND OBJECTIVES Vascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3-5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models. RESULTS VC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to 2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were independently related to AS≥3. After a median follow-up of 35 months (interquartile range=17-36), there were 70 deaths (10%). After multivariate adjustment for age, smoking, diabetes, comorbidity, renal function, and level of phosphorous, AS≥3 but not KS>6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event-free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC did not predict renal progression. CONCLUSIONS VC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful index to identify patients with CKD at high risk of death and morbidity as previously reported in patients on dialysis.
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Affiliation(s)
- José L Górriz
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
| | - Pablo Molina
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - M Jesús Cerverón
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Rocío Vila
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Jordi Bover
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Javier Nieto
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Guillermina Barril
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Alberto Martínez-Castelao
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Elvira Fernández
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Verónica Escudero
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Celestino Piñera
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Teresa Adragao
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Juan F Navarro-Gonzalez
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Luis M Molinero
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Cristina Castro-Alonso
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Luis M Pallardó
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
| | - Sophie A Jamal
- Due to the number of contributing authors, the affiliations are provided in the Supplemental Material
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Martín M, Valls J, Betriu A, Fernández E, Valdivielso JM. Association of serum phosphorus with subclinical atherosclerosis in chronic kidney disease. Sex makes a difference. Atherosclerosis 2015; 241:264-70. [PMID: 25748053 DOI: 10.1016/j.atherosclerosis.2015.02.048] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Revised: 02/20/2015] [Accepted: 02/20/2015] [Indexed: 11/25/2022]
Abstract
BACKGROUND Cardiovascular disease is the leading cause of mortality in chronic kidney disease (CKD). Serum phosphate has been associated to cardiovascular disease in the general population and this effect seems to be different according to sex. In the present study we analyze the effect of phosphate on subclinical atherosclerosis in the NEFRONA population and its effect depending on sex. DESIGN Carotid ultrasound assessing the presence of plaques was performed by an itinerant team in 1687 CKD patients not in dialysis without previous cardiovascular events. Standard blood test and anthropometrical parameters were also recorded. RESULTS Multivariate linear regression to model phosphate levels in patients with CKD showed an interaction of sex with age. Thus, among men, serum phosphate levels declined significantly with age almost linearly. Serum phosphate levels in women under the age of 40-45 years overlapped with those in men and then stayed above, showing and overall constant relationship. Multivariate logistic regression analysis showed that higher phosphate levels associated with a higher risk of presenting atheromatous plaque. This risk however was different according to sex. In men, phosphate levels within the normal range associated with an increased risk of subclinical atheromatosis whereas in women this risk only increased with serum levels over the normal range. CONCLUSIONS This study demonstrates that phosphate levels are associated with the presence of subclinical atheromatosis in a large CKD population. This effect of phosphate on subclinical atheromatosis was different according to sex, suggesting that a recommended serum phosphate levels could be different for male than for female CKD patients.
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Affiliation(s)
- Marisa Martín
- Nephrology Service and Unit for the Detection and Treatment of Atherothrombotic Diseases (UDETMA), Hospital Universitari Arnau de Vilanova, IRBLLEIDA. Av. Rovira Roure 80, 25198 Lleida, Spain.
| | - Joan Valls
- Biostatistics Unit, IRBLLEIDA. Av. Rovira Roure 80, 25198 Lleida, Spain
| | - Angels Betriu
- Nephrology Service and Unit for the Detection and Treatment of Atherothrombotic Diseases (UDETMA), Hospital Universitari Arnau de Vilanova, IRBLLEIDA. Av. Rovira Roure 80, 25198 Lleida, Spain
| | - Elvira Fernández
- Nephrology Service and Unit for the Detection and Treatment of Atherothrombotic Diseases (UDETMA), Hospital Universitari Arnau de Vilanova, IRBLLEIDA. Av. Rovira Roure 80, 25198 Lleida, Spain
| | - Jose M Valdivielso
- Experimental Nephrology Laboratory, IRBLLEIDA. Av. Rovira Roure 80, 25198 Lleida, Spain.
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Arroyo D, Betriu A, Martinez-Alonso M, Vidal T, Valdivielso JM, Fernández E. Observational multicenter study to evaluate the prevalence and prognosis of subclinical atheromatosis in a Spanish chronic kidney disease cohort: baseline data from the NEFRONA study. BMC Nephrol 2014; 15:168. [PMID: 25326683 PMCID: PMC4210528 DOI: 10.1186/1471-2369-15-168] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Accepted: 10/02/2014] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Cardiovascular events (CVE) are more prevalent in chronic kidney disease (CKD) than in general population, being the main cause of morbimortality. Specific risk factors related to CKD have been suggested, because traditional factors do not fully explain this increase in cardiovascular disease rates. However, the role of atheromatosis, its pathogenesis and evolution are still unclear. The potential use of diagnostic tests to detect subclinical atheromatosis has to be determined. METHODS NEFRONA is a prospective multicenter cohort study. 2445 CKD subjects were enrolled from 81 Spanish hospitals and dialysis clinics, from 2010 to 2012. Eligibility criteria included: 18 to 74 years old, CKD stage 3 or higher, and no previous CVE. 559 non-CKD controls were also recruited. Demographical, clinical and analytical data were collected. Carotid and femoral ultrasounds were performed by a single trained team to measure carotid intima-media thickness (cIMT) and detect atheromatous plaques. Ankle-brachial index (ABI) was measured. RESULTS Differences in age, sex and prevalence and control of cardiovascular risk factors were found between controls and CKD patients. These differences are similar to those described in epidemiological studies.No difference was found regarding cIMT between controls and CKD (when subjects with plaques in common carotid arteries were omitted); earlier CKD stages had higher values. CKD patients had a higher rate of atheromatous plaques, with no difference between stages in the unadjusted analysis. A group of patients had plaques in femoral arteries but were plaque-free in carotid arteries, and would have gone underdiagnosed without the femoral study. The percentage of pathologic ABI was higher in CKD, with higher prevalence in more advanced stages, and a higher rate of ABI >1.4 than <0.9, suggesting more vascular calcification. CONCLUSIONS NEFRONA is the first large study describing the actual prevalence of subclinical atheromatosis across different CKD stages. There is a very high rate of atheromatous plaques and pathologic ABI in CKD. Prospective data will add important information to the pathogenesis and evolution of atheromatosis in CKD, compared to non-CKD subjects.
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Affiliation(s)
- David Arroyo
- Nephrology Department, Hospital Universitari Arnau de Vilanova, Avda, Rovira Roure 80, 25198 Lleida, Spain.
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Yamada S, Oshima M, Watanabe Y, Miyake H. Arterial location-specific calcification at the carotid artery and aortic arch for chronic kidney disease, diabetes mellitus, hypertension, and dyslipidemia. Calcif Tissue Int 2014; 95:267-74. [PMID: 25017195 DOI: 10.1007/s00223-014-9891-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2014] [Accepted: 06/26/2014] [Indexed: 11/30/2022]
Abstract
Several risk factors for arterial calcification have been reported but controversial. The aim of this study was to clarify the interactions among chronic kidney disease (CKD), diabetes mellitus (DM), hypertension, and dyslipidemia in altering the risk of arterial calcification in the three different arterial locations and the intramural location at the internal carotid artery (ICA) origins. Calcified burdens at the ICA origins, the aortic arch, and its orifices were evaluated in a retrospective fashion by using computed tomography angiography in 397 patients. The multivariate analyses were adjusted for age, gender, CKD, DM, hypertension, dyslipidemia, and current smoking status. Additionally, subgroup analyses in each variable were conducted. Our multivariate logistic regression analyses revealed that CKD was significantly associated with the outside-wall calcification at the ICA origins, whereas DM was only associated with the inside-ICA-wall calcification. Additionally, we found that DM increased the association between CKD and arterial calcification at the aortic arch and its orifices, and the outside-wall at the ICA origins. Hypertension was significantly associated with the calcification at the orifices of the aortic arch branches synergistically with CKD. Dyslipidemia did not have any significant association with calcification in any of the three vascular beds. CKD had the highest prevalence risk of calcification in common with the three different vascular beds. CKD in combination with DM, as well as hypertension in combination with CKD, were key relationships affecting the risk of arterial calcification, especially at the aortic arch and its orifices.
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Affiliation(s)
- Shigeki Yamada
- Department of Neurosurgery & Stroke Center, Rakuwakai Otowa Hospital, Otowachinji-cho 2, Yamashina-ku, Kyoto, 607-8602, Japan,
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Basile C, Lomonte C, Lisi P, Karohl C, Di Iorio B, Bellasi A. Physical activity in chronic kidney disease: a plausible approach to vascular calcification? Kidney Blood Press Res 2014; 39:154-63. [PMID: 25117909 DOI: 10.1159/000355791] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/11/2014] [Indexed: 11/19/2022] Open
Abstract
Vascular calcification (VC) is a prominent feature that affects up to 40 to 80% of Chronic Kidney Disease (CKD) patients depending on the degree of renal impairment. Though etiology and pathogenesis of the different types of VC are far from being elucidated, it is conceivable that an imbalance between promoters and inhibitors represents the condition that triggers VC deposition and progression. In addition to traditional cardiovascular risk factors, several lines of evidence suggest that specific factors may affect the arterial system and prognosis in CKD. Over the last decade, a few pharmacological strategies aimed at controlling different selected risk factors for VC have been investigated yielding conflicting results. In light of the complicated interplay between inhibitors and promoters as well as the fact that VC represents the result of cumulative and prolonged exposure to multiple risk factors, a more comprehensive risk modification approach such as lifestyle modification or physical activity (PA) may represent a valid strategy to attenuate VC deposition and progression.We herein aim at reviewing the rationale and current evidence on the potential for lifestyle modification with a specific focus on PA as a cost-effective strategy for VC treatment.
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Affiliation(s)
- Carlo Basile
- Division of Nephrology, Miulli General Hospital, Acquaviva delle Fonti (BA), Italy
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Valcheva P, Cardus A, Panizo S, Parisi E, Bozic M, Lopez Novoa JM, Dusso A, Fernández E, Valdivielso JM. Lack of vitamin D receptor causes stress-induced premature senescence in vascular smooth muscle cells through enhanced local angiotensin-II signals. Atherosclerosis 2014; 235:247-55. [PMID: 24880896 DOI: 10.1016/j.atherosclerosis.2014.05.911] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2014] [Revised: 04/09/2014] [Accepted: 05/01/2014] [Indexed: 12/20/2022]
Abstract
OBJECTIVES The inhibition of the renal renin-angiotensin system by the active form of vitamin D contributes to the cardiovascular health benefits of a normal vitamin D status. Local production of angiotensin-II in the vascular wall is a potent mediator of oxidative stress, prompting premature senescence. Herein, our objective was to examine the impact of defective vitamin D signalling on local angiotensin-II levels and arterial health. METHODS Primary cultures of aortic vascular smooth muscle cells (VSMC) from wild-type and vitamin D receptor-knockout (VDRKO) mice were used for the assessment of cell growth, angiotensin-II and superoxide anion production and expression levels of cathepsin D, angiotensin-II type 1 receptor and p57(Kip2). The in vitro findings were confirmed histologically in aortas from wild-type and VDRKO mice. RESULTS VSMC from VDRKO mice produced more angiotensin-II in culture, and elicited higher levels of cathepsin D, an enzyme with renin-like activity, and angiotensin-II type 1 receptor, than wild-type mice. Accordingly, VDRKO VSMC showed higher intracellular superoxide anion production, which could be suppressed by cathepsin D, angiotensin-II type 1 receptor or NADPH oxidase antagonists. VDRKO cells presented higher levels of p57(Kip2), impaired proliferation and premature senescence, all of them blunted upon inhibition of angiotensin-II signalling. In vivo studies confirmed higher levels of cathepsin D, angiotensin-II type 1 receptor and p57(Kip2) in aortas from VDRKO mice. CONCLUSION The beneficial effects of active vitamin D in vascular health could be a result of the attenuation of local production of angiotensin-II and downstream free radicals, thus preventing the premature senescence of VSMC.
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Affiliation(s)
- Petya Valcheva
- Experimental Nephrology Laboratory, Department of Experimental Medicine, Biomedical Research Institute of Lleida (IRBLLEIDA), Lleida, Spain
| | - Anna Cardus
- Experimental Nephrology Laboratory, Department of Experimental Medicine, Biomedical Research Institute of Lleida (IRBLLEIDA), Lleida, Spain
| | - Sara Panizo
- Experimental Nephrology Laboratory, Department of Experimental Medicine, Biomedical Research Institute of Lleida (IRBLLEIDA), Lleida, Spain
| | - Eva Parisi
- Experimental Nephrology Laboratory, Department of Experimental Medicine, Biomedical Research Institute of Lleida (IRBLLEIDA), Lleida, Spain
| | - Milica Bozic
- Experimental Nephrology Laboratory, Department of Experimental Medicine, Biomedical Research Institute of Lleida (IRBLLEIDA), Lleida, Spain
| | - Jose M Lopez Novoa
- Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain
| | - Adriana Dusso
- Experimental Nephrology Laboratory, Department of Experimental Medicine, Biomedical Research Institute of Lleida (IRBLLEIDA), Lleida, Spain
| | - Elvira Fernández
- Nephrology Service and UDETMA, University Hospital Arnau de Vilanova, Lleida, Spain
| | - Jose M Valdivielso
- Experimental Nephrology Laboratory, Department of Experimental Medicine, Biomedical Research Institute of Lleida (IRBLLEIDA), Lleida, Spain.
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Long-term Morbidity and Mortality of Carotid Endarterectomy in Patients with End-stage Renal Disease Receiving Hemodialysis. J Stroke Cerebrovasc Dis 2014; 23:545-9. [DOI: 10.1016/j.jstrokecerebrovasdis.2013.05.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2013] [Revised: 05/07/2013] [Accepted: 05/10/2013] [Indexed: 11/21/2022] Open
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Yamada S, Oshima M, Watanabe Y, Ogata H, Hashimoto K, Miyake H. Intramural location and size of arterial calcification are associated with stenosis at carotid bifurcation. Eur J Radiol 2014; 83:957-963. [PMID: 24637069 DOI: 10.1016/j.ejrad.2014.02.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2013] [Accepted: 02/08/2014] [Indexed: 11/17/2022]
Abstract
PURPOSE The purpose of this study was to investigate the association between internal carotid artery (ICA) stenosis and intramural location and size of calcification at the ICA origins and the origins of the cervical arteries proximal to the ICA. METHOD A total of 1139 ICAs were evaluated stenosis and calcification on the multi-detector row CT angiography. The intramural location was categorized into none, outside and inside location. The calcification size was evaluated on the 4-point grading scale. The multivariate analyses were adjusted for age, serum creatinine level, hypertension, hyperlipidemia, diabetes mellitus, smoking and alcohol habits. RESULTS Outside calcification at the ICA origins showed the highest multivariate odds ratio (OR) for the presence of ICA stenosis (30.0) and severe calcification (a semicircle or more of calcification at the arterial cross-sectional surfaces) did the second (14.3). In the subgroups of >70% ICA stenosis, the multivariate OR of outside location increased to 44.8 and that of severe calcification also increased to 32.7. Four of 5 calcified carotid plaque specimens extracted by carotid endarterectomy were histologically confirmed to be calcified burdens located outside the internal elastic lamia which were defined as arterial medial calcification. CONCLUSIONS ICA stenosis was strongly associated with severe calcification located mainly outside the carotid plaque. Outside calcification at the ICA origins should be evaluated separately from inside calcification, as a marker for the ICA stenosis. Additionally, we found that calcification at the origins of the cervical arteries proximal to the ICA was significantly associated with the ICA stenosis.
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Affiliation(s)
- Shigeki Yamada
- Department of Neurosurgery & Stroke Center, Rakuwakai Otowa Hospital, Otowachinji-cho 2, Yamashina-ku, Kyoto 607-8602, Japan; Department of Neurosurgery, Hamamatsu Rosai Hospital, 25 Shogen-cho, Higashi-ku, Hamamatsu city, Shizuoka 430-8525, Japan; Interfaculty Initiative in Information Studies/Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.
| | - Marie Oshima
- Interfaculty Initiative in Information Studies/Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505, Japan.
| | - Yoshihiko Watanabe
- Department of Neurosurgery, Hamamatsu Rosai Hospital, 25 Shogen-cho, Higashi-ku, Hamamatsu city, Shizuoka 430-8525, Japan.
| | - Hideki Ogata
- Department of Neurosurgery, Hamamatsu Rosai Hospital, 25 Shogen-cho, Higashi-ku, Hamamatsu city, Shizuoka 430-8525, Japan.
| | - Kenji Hashimoto
- Department of Neurosurgery, Kishiwada Municipal Hospital, 1001 Gakuhara-cho, Kishiwada city, Osaka 596-8501, Japan.
| | - Hidenori Miyake
- Department of Neurosurgery, Hamamatsu Rosai Hospital, 25 Shogen-cho, Higashi-ku, Hamamatsu city, Shizuoka 430-8525, Japan.
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Craver L, Dusso A, Martinez-Alonso M, Sarro F, Valdivielso JM, Fernández E. A low fractional excretion of Phosphate/Fgf23 ratio is associated with severe abdominal Aortic calcification in stage 3 and 4 kidney disease patients. BMC Nephrol 2013; 14:221. [PMID: 24119158 PMCID: PMC3852798 DOI: 10.1186/1471-2369-14-221] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Accepted: 10/09/2013] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Vascular calcification (VC) contributes to high mortality rates in chronic kidney disease (CKD). High serum phosphate and FGF23 levels and impaired phosphaturic response to FGF23 may affect VC. Therefore, their relative contribution to abdominal aortic calcification (AAC) was examined in patients CKD stages 3-4. METHODS Potential risk factors for AAC, measured by the Kauppila Index (KI), were studied in 178 patients. RESULTS In multivariate linear analysis, AAC associated positively with age, male gender, CKD-stage, presence of carotid plaques (CP) and also with FGF23, but negatively with fractional excretion of phosphate (FEP). Intriguingly, FEP increased with similar slopes with elevations in PTH, with reductions in GFR, and also with elevations in FGF23 but the latter only in patients with none (KI = 0) or mild (KI = 1-5) AAC. Lack of a FEP-FGF23 correlation in patients with severe AAC (KI > 5) suggested a role for an impaired phosphaturic response to FGF23 but not to PTH in AAC. Logistic and zero-inflated analysis confirmed the independent association of age, CKD stage, male gender and CP with AAC, and also identified a threshold FEP/FGF23 ratio of 1/3.9, below which the chances for a patient of presenting severe AAC increased by 3-fold. Accordingly, KI remained unchanged as FEP/FGF23 ratios decreased from 1/1 to 1/3.9 but markedly increased in parallel with further reductions in FEP/FGF23 < 1/3.9. CONCLUSIONS In CKD 3-4, an impaired phosphaturic response to FGF23 with FEP/FGF23 < 1/3.9 associates with severe AAC independently of age, gender or CP.
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Affiliation(s)
- Lourdes Craver
- Nephrology Service and Unit for the Detection and Treatment of Atherothrombotic diseases (UDETMA), Hospital Universitari Arnau de Vilanova, Av Rovira Roure, 25198 Lleida, Spain.
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Association of serum fetuin-A and fetuin-A gene polymorphism in relation to mineral and bone disorders in patients with chronic kidney disease. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2013. [DOI: 10.1016/j.ejmhg.2013.07.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
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Marinelli A, Pistolesi V, Pasquale L, Di Lullo L, Ferrazzano M, Baudena G, Della Grotta F, Di Napoli A. Diagnosis of Arterial Media Calcification in Chronic Kidney Disease. Cardiorenal Med 2013; 3:89-95. [PMID: 23922548 DOI: 10.1159/000350764] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2013] [Accepted: 03/04/2013] [Indexed: 11/19/2022] Open
Abstract
PURPOSE Arterial media calcification (AMC) is often the only vascular calcification (VC) present in young patients with chronic renal failure and its presence is associated with higher mortality rates. Currently, X-ray imaging (as a standard approach) is able to show AMC in areas without diffuse overlapping arterial intimal calcification (AIC), but X-ray imaging only allows us to identify this lesion when the vessel is widely calcified. The aim of this study was to evaluate the possibility of using ultrasonography as opposed to X-rays to visualize AMC in patients with chronic renal failure. Patients and Methods: In this cross-sectional study, we examined 105 patients (chronic kidney disease stage IV: 19 patients, hemodialysis: 48 patients, renal transplant: 26 patients; mean age: 54 ± 14 years; 65 males and 40 females); B-mode ultrasonography was performed to detect AMC or AIC on the superficial femoral artery (SFA). As a control, plain radiography of the thigh was performed in all patients. RESULTS Upon ultrasonography investigation, 12 subjects were excluded due to diffuse VC on the SFA that did not permit a distinction between AMC and AIC. In the remaining 93 patients, AMC was detected on the SFA in 43 patients using ultrasonography and in 20 patients using the standard approach. The sensitivity and specificity of the standard approach for the detection of AMC on the SFA were 47 and 100%, respectively. The positive and negative predictive values of the standard approach were 1 and 0.68, respectively. CONCLUSION Ultrasonography is able to detect AMC better than the X-ray approach, focusing on individuals at higher risk.
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Cianciolo G, La Manna G, Della Bella E, Cappuccilli ML, Angelini ML, Dormi A, Capelli I, Laterza C, Costa R, Alviano F, Donati G, Ronco C, Stefoni S. Effect of vitamin D receptor activator therapy on vitamin D receptor and osteocalcin expression in circulating endothelial progenitor cells of hemodialysis patients. Blood Purif 2013; 35:187-95. [PMID: 23485859 DOI: 10.1159/000347102] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2012] [Accepted: 01/15/2013] [Indexed: 01/05/2023]
Abstract
BACKGROUND The effects of vitamin D receptor (VDR) and osteocalcin (OC) expression as well as VDR agonist (VDRA) therapy on circulating endothelial progenitor cells (EPCs) has not been elucidated yet. METHODS We therefore analyzed EPCs in 30 healthy controls and 82 patients undergoing dialysis (no VDRA therapy: 28; oral calcitriol: 30, and intravenous paricalcitol, PCTA: 24). The percentage of EPCs (CD34+/CD133-/KDR+/CD45-) expressing VDR or OC, and VDR and OC expression defined by mean fluorescence intensity (MFI) were analyzed using flow cytometry. The in vitro effect of VDRAs was evaluated in EPCs isolated from each patient group. RESULTS The percentage of VDR+ EPCs correlated positively with VDRA therapy and 25(OH)D, and negatively with diabetes, C-reactive protein, hemoglobin and osteopontin. VDR-MFI correlated positively with VDRA therapy, parathyroid hormone (PTH) and 25(OH)D, and negatively with diabetes and osteopontin. The percentage of OC+ EPCs correlated positively with the calcium score, PTH and phosphate, and negatively with 25(OH)D. OC-MFI correlated positively with calcium score, PTH, phosphate and hemoglobin, and negatively with albumin, 25(OH)D and osteopontin. Cell cultures from patients without VDRA therapy had the highest levels of calcium deposition and OC expression, which both significantly decreased following in vitro VDRA administration: in particular extracellular calcium deposition was only reduced by adding PCTA. CONCLUSIONS Our data suggest that 25(OH)D serum levels and VDRA therapy influence VDR and OC expression on circulating EPCs. Since OC expression may contribute to vascular calcification, we hypothesize a putative protective role of VDRA therapy.
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Affiliation(s)
- Giuseppe Cianciolo
- Section of Nephrology, Department of Internal Medicine, Aging and Renal Disease, University of Bologna, Bologna, Italy
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Tan CS, Fintelmann F, Joe J, Ganguli S, Wu S. Coronary-subclavian steal syndrome in a hemodialysis patient, a case report and review of literature. Semin Dial 2013; 26:E42-6. [PMID: 23458240 DOI: 10.1111/sdi.12077] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Dialysis vascular access associated coronary-subclavian steal or hypoperfusion syndrome is an uncommon but potentially life threatening condition. Awareness of this syndrome is important in the management of vascular access in hemodialysis patients. We report a case of dialysis vascular access associated coronary-subclavian steal syndrome and review the literature on its pathogenesis and therapeutic implications.
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Affiliation(s)
- Chieh Suai Tan
- Vascular Imaging and Intervention Division, Massachusetts General Hospital, Harvard Medical School Division of Nephrology, Massachusetts General Hospital, Harvard Medical School Department of Medicine, Massachusetts General Hospital, Harvard Medical School Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
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Abstract
PURPOSE OF REVIEW The chronic kidney disease (CKD) mineral bone disorder syndrome encompasses a number of metabolic, bone as well as vascular abnormalities of which vascular calcification is a prominent feature. Several noninvasive imaging techniques provide physicians with useful prognostic information beyond traditional cardiovascular and CKD-specific risk factors. We review the most recent evidence on vascular calcification screening as a tool for risk stratification in CKD patients. RECENT FINDINGS Cardiovascular aging is accelerated and is associated with a poor prognosis in CKD patients. Numerous traditional and nontraditional risk factors have been associated with this outcome. Imaging markers and serological risk factors do not carry the same prognostic information. In fact, whereas serum biomarkers reflect the risk to which the individual is exposed at the time of measurement, imaging markers represent the cumulative result of prolonged exposure to one or multiple risk factors. As such, they have often been demonstrated to be better outcome predictors than serological markers. In some cases, imaging markers have been suggested as desirable targets of therapy or to guide treatment individualization. SUMMARY Recent evidence suggests that cardiovascular imaging allows for cardiovascular risk stratification and treatment individualization in CKD patients.
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Dégi A, Kerti A, Kis E, Cseprekál O, Tory K, Szabó AJ, Reusz GS. Cardiovascular risk assessment in children following kidney transplantation. Pediatr Transplant 2012; 16:564-76. [PMID: 22694162 DOI: 10.1111/j.1399-3046.2012.01730.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
CV diseases are the leading cause of death among patients with ESRD. RTX decreases the CV risk; however, it still remains definitely higher than that of the general population. Large multicenter and longitudinal studies are difficult to perform and hard end-points of CV events are usually missing among pediatric population. Thus, appropriate estimation of CV risk is of crucial importance to define the potential hazards and to evaluate the effect of treatments aimed to reduce the risk. A number of validated non-invasive methods are available to assess the extent of CV damage in adults, such as calcification scores, cIMT, aPWV, 24-h ABPM, AASI, and HRV; however, they need adaptation, standardization, and validation in pediatric studies. cIMT and PWV are the most promising methods, as pediatric normative values are already present. The up-to-date treatment of ESRD aims not only to save life, but to offer the patient a life expectancy approaching that of the healthy population and to ensure a reasonable quality of life.
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Affiliation(s)
- Arianna Dégi
- First Department of Pediatrics, Semmelweis University, Budapest, Hungary
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Malík J, Kudlička J, Tuka V, Chytilová E, Adamec J, Ročínová K, Tesař V. Common carotid wall shear stress and carotid atherosclerosis in end-stage renal disease patients. Physiol Res 2012; 61:355-61. [PMID: 22670700 DOI: 10.33549/physiolres.932259] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Decrease of arterial wall shear stress (WSS) is associated with higher probability of atherosclerotic plaque development in many disease conditions. End-stage renal diseases (ESRD) patients suffer from vascular disease frequently, but its nature differs from general population. This study was aimed at proving an association between common carotid wall shear stress and the presence of carotid bifurcation plaques in a group of ESRD patients. ESRD subjects, planned for the creation of a dialysis access and therapy were included. Wall shear rate (WSR) was used as a surrogate of WSS and was analyzed in the common carotid arteries by duplex ultrasonography. Intima media thickness (IMT) was measured at the same site. The presence/absence of carotid bifurcation plaques was recorded. The endothelial function was estimated by the levels of von Willebrand factor (vWf). 35 ESRD patients were included (19 females, 17 diabetics). Atherosclerotic plaque was present in 53 % of bifurcations. Wall shear rate was lower in arteries with plaques (349+/-148 vs. 506+/-206 s(-1), p=0.005) and was directly related to the height of IMT and inversely to the activity of vWf (r= -0.65, p=0.016). Lower wall shear rate in the common carotid arteries is linked to the endothelial dysfunction and to the presence of atherosclerotic plaques in carotid bifurcations in ESRD subjects. Faster arterial dilatation may facilitate this process in ESRD subjects.
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Affiliation(s)
- J Malík
- Third Department of Internal Medicine, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
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Osorio A, Ortega E, Torres JM, Sanchez P, Ruiz-Requena E. Mineral-bone metabolism markers in young hemodialysis patients. Clin Biochem 2011; 44:1425-8. [DOI: 10.1016/j.clinbiochem.2011.08.1143] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2011] [Revised: 07/28/2011] [Accepted: 08/28/2011] [Indexed: 10/17/2022]
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